Trial Outcomes & Findings for ALL Adult Consortium Trial: Adult ALL Trial (NCT NCT00476190)

Participant milestones
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
Overall Study STARTED	66	46
Overall Study Eligible and Treated	65	45
Overall Study Treated and Toxicity Data Reported	66	44
Overall Study Eligible and Treated and Toxicity Data Reported	65	44
Overall Study Evaluable for Complete Remission	64	39
Overall Study Achieved Complete Remission	57	34
Overall Study Proceeded to Stem Cell Transplant (SCT)	15	6
Overall Study Initiated Asparaginase Consolidation Therapy	42	28
Overall Study COMPLETED	25	20
Overall Study NOT COMPLETED	41	26

Reasons for withdrawal
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
Overall Study Ineligible	1	1
Overall Study Induction Death	2	0
Overall Study Induction Failure	2	4
Overall Study Lost to Follow-up	1	0
Overall Study Relapse/Progression	5	2
Overall Study Remission Death	0	1
Overall Study Transplant in first Complete Remission (CR)	15	6
Overall Study Withdrawal by Subject	6	2
Overall Study Other	9	10

Baseline characteristics by cohort
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=65 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=45 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Total n=110 Participants Total of all reporting groups
Age, Customized 18-19 years	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Age, Customized 20-29 years	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Age, Customized 30-39 years	19 Participants n=5 Participants	11 Participants n=7 Participants	30 Participants n=5 Participants
Age, Customized 40-50 years	20 Participants n=5 Participants	13 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	18 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	27 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	56 Participants n=5 Participants	37 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	58 Participants n=5 Participants	30 Participants n=7 Participants	88 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Immunophenotype B-cell	56 Participants n=5 Participants	34 Participants n=7 Participants	90 Participants n=5 Participants
Immunophenotype T-cell	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) <30	48 Participants n=5 Participants	33 Participants n=7 Participants	81 Participants n=5 Participants
White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) >=30	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
White Blood Count (WBC) (x10 ^-3) at diagnosis (cells/uL) Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 1 (-) CSF WBC <5 without blasts	40 Participants n=5 Participants	37 Participants n=7 Participants	77 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 2 (+) CSF WBC <5 with blasts	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 3 (+) CSF WBC ≥5 with blasts	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis Traumatic Tap with Blasts	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis Traumatic Tap without Blasts	12 Participants n=5 Participants	2 Participants n=7 Participants	14 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis Not performed	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Risk Classification Standard Risk (SR)	31 Participants n=5 Participants	25 Participants n=7 Participants	56 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Risk Classification High Risk (HR)	34 Participants n=5 Participants	20 Participants n=7 Participants	54 Participants n=5 Participants

Outcome measures
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=42 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=28 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
Asparaginase Completion Rate	43 Percentage of patients Interval 32.0 to 54.0	79 Percentage of patients Interval 65.0 to 88.0

Outcome measures
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=65 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=44 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
Number of Participants With Grade 3 or Worse Toxicity. Neutrophils	49 participants	31 participants
Number of Participants With Grade 3 or Worse Toxicity. Platelets	44 participants	30 participants
Number of Participants With Grade 3 or Worse Toxicity. Febrile neutropenia	30 participants	23 participants
Number of Participants With Grade 3 or Worse Toxicity. Infection with grade 3/4 neutropenia	24 participants	10 participants
Number of Participants With Grade 3 or Worse Toxicity. Infection, other	5 participants	3 participants
Number of Participants With Grade 3 or Worse Toxicity. AST	19 participants	5 participants
Number of Participants With Grade 3 or Worse Toxicity. ALT	34 participants	13 participants
Number of Participants With Grade 3 or Worse Toxicity. Bilirubin	24 participants	3 participants
Number of Participants With Grade 3 or Worse Toxicity. Liver dysfunction/failure	2 participants	1 participants
Number of Participants With Grade 3 or Worse Toxicity. Hyperglycemia	10 participants	8 participants
Number of Participants With Grade 3 or Worse Toxicity. Stomatitis	8 participants	2 participants
Number of Participants With Grade 3 or Worse Toxicity. CNS hemorrhage	2 participants	0 participants
Number of Participants With Grade 3 or Worse Toxicity. Thrombosis	19 participants	7 participants
Number of Participants With Grade 3 or Worse Toxicity. Seizure	5 participants	0 participants
Number of Participants With Grade 3 or Worse Toxicity. Osteonecrosis	4 participants	1 participants
Number of Participants With Grade 3 or Worse Toxicity. Hypersensitivity	3 participants	6 participants
Number of Participants With Grade 3 or Worse Toxicity. Pancreatitis	1 participants	2 participants
Number of Participants With Grade 3 or Worse Toxicity. Neuropathy	5 participants	4 participants

Outcome measures
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=64 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=39 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
Complete Remission Rate	57 Participants	34 Participants

Outcome measures
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=57 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=34 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
3-year Disease Free Survival	70 Percentage of patients Interval 56.0 to 81.0	75 Percentage of patients Interval 53.0 to 88.0

Outcome measures
Measure	Pre-amendment Cohort, 2500 IU/m2 q2 Weeks n=65 Participants The first 66 patients enrolled under the initial design. In the post-induction phases, IV asparaginase was administered every two weeks at the higher dose of 2500 IU/m2, for a total of 30 post-induction weeks. IV asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.	Post-amendment Cohort, 2000 IU/m2 q3 Weeks n=45 Participants The 46 patients enrolled under amended design, after August 1, 2011. In the post-induction phases, IV asparaginase was administered every 3 weeks at the dose of 2000 IU/m2, for a total of 30 post-induction weeks. E. coli asparaginase was administered as a single dose during induction. Protocol therapy was comprised of 6 phases: Prophase, Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.
3-year Overall Survival	70 Percentage of patients Interval 57.0 to 80.0	83 Percentage of patients Interval 67.0 to 91.0

Blood and lymphatic system disorders

Anemia

63.6%

42/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

43.2%

19/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Blood and lymphatic system disorders

Blood and lymphatic system disorders - Other, specify

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Blood and lymphatic system disorders

Disseminated intravascular coagulation

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Blood and lymphatic system disorders

Febrile neutropenia

50.0%

33/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

61.4%

27/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Blood and lymphatic system disorders

Hemolysis

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Atrial fibrillation

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Cardiac disorders - Other, specify

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Chest pain - cardiac

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Left ventricular systolic dysfunction

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Palpitations

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Paroxysmal atrial tachycardia

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Pericardial effusion

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Pericarditis

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Sinus bradycardia

24.2%

16/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Supraventricular tachycardia

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Ventricular arrhythmia

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Cardiac disorders

Ventricular tachycardia

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

Ear and labyrinth disorders - Other, specify

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

Ear pain

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

External ear pain

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

Hearing impaired

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

Middle ear inflammation

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Ear and labyrinth disorders

Tinnitus

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Endocrine disorders

Adrenal insufficiency

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Endocrine disorders

Cushingoid

16.7%

11/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Endocrine disorders

Endocrine disorders - Other, specify

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Endocrine disorders

Hypothyroidism

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Blurred vision

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Cataract

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Dry eye

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Extraocular muscle paresis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Eye disorders - Other, specify

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Eye pain

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Flashing lights

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Papilledema

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Photophobia

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Eye disorders

Watering eyes

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Abdominal distension

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Abdominal pain

60.6%

40/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

54.5%

24/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Anal fistula

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Anal pain

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Anal ulcer

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Colitis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Colonic perforation

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Constipation

48.5%

32/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

52.3%

23/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Dental caries

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Diarrhea

60.6%

40/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

50.0%

22/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Dry mouth

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Dyspepsia

37.9%

25/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

31.8%

14/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Dysphagia

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Enterocolitis

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Esophageal pain

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Esophageal ulcer

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Esophagitis

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Fecal incontinence

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Flatulence

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Gastric ulcer

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Gastritis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Gastrointestinal disorders - Other, specify

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

38.6%

17/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Gingival pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Hemorrhoids

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

25.0%

11/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Lower gastrointestinal hemorrhage

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Mucositis oral

42.4%

28/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

40.9%

18/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Nausea

83.3%

55/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

84.1%

37/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Oral hemorrhage

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Oral pain

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Pancreatitis

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Periodontal disease

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Proctitis

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Rectal hemorrhage

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Rectal pain

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Stomach pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Toothache

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Typhlitis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Upper gastrointestinal hemorrhage

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Gastrointestinal disorders

Vomiting

72.7%

48/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

54.5%

24/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Chills

25.8%

17/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Death NOS

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Edema face

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Edema limbs

51.5%

34/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

31.8%

14/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Edema trunk

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Fatigue

81.8%

54/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

72.7%

32/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Fever

28.8%

19/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

36.4%

16/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Flu like symptoms

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Gait disturbance

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

General disorders and administration site conditions - Other, specify

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Injection site reaction

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Localized edema

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Non-cardiac chest pain

15.2%

10/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

General disorders

Pain

40.9%

27/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

34.1%

15/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Hepatobiliary disorders

Cholecystitis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Hepatobiliary disorders

Hepatic failure

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Hepatobiliary disorders

Hepatic pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Hepatobiliary disorders

Hepatobiliary disorders - Other, specify

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Immune system disorders

Allergic reaction

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

34.1%

15/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Immune system disorders

Immune system disorders - Other, specify

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Abdominal infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Bone infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Bronchial infection

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Catheter related infection

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Conjunctivitis infective

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Encephalomyelitis infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Enterocolitis infectious

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Eye infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Gum infection

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Infections and infestations - Other, specify

63.6%

42/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

61.4%

27/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Kidney infection

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Lip infection

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Lung infection

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Nail infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Otitis externa

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Otitis media

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Penile infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Peripheral nerve infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Pharyngitis

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Rhinitis infective

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Sepsis

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Sinusitis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Skin infection

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Upper respiratory infection

13.6%

9/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Urinary tract infection

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Vaginal infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Infections and infestations

Wound infection

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Bruising

19.7%

13/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Dermatitis radiation

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Esophageal anastomotic leak

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Fracture

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Intraoperative skin injury

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Radiation recall reaction (dermatologic)

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Vascular access complication

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Injury, poisoning and procedural complications

Wound dehiscence

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Activated partial thromboplastin time prolonged

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Alanine aminotransferase increased

68.2%

45/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

52.3%

23/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Alkaline phosphatase increased

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Aspartate aminotransferase increased

54.5%

36/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

38.6%

17/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Blood bilirubin increased

57.6%

38/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

CPK increased

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Cardiac troponin I increased

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Cholesterol high

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Creatinine increased

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Electrocardiogram QT corrected interval prolonged

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Fibrinogen decreased

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

GGT increased

15.2%

10/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

INR increased

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Investigations - Other, specify

33.3%

22/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Lipase increased

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Lymphocyte count decreased

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

31.8%

14/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Neutrophil count decreased

74.2%

49/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

70.5%

31/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Platelet count decreased

71.2%

47/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

72.7%

32/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Serum amylase increased

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Weight gain

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

Weight loss

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Investigations

White blood cell decreased

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

38.6%

17/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Acidosis

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Anorexia

51.5%

34/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

34.1%

15/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Dehydration

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Glucose intolerance

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypercalcemia

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hyperglycemia

50.0%

33/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

34.1%

15/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hyperkalemia

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypermagnesemia

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypernatremia

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypertriglyceridemia

34.8%

23/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

36.4%

16/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hyperuricemia

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypoalbuminemia

25.8%

17/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypocalcemia

24.2%

16/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypoglycemia

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypokalemia

34.8%

23/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypomagnesemia

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hyponatremia

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Hypophosphatemia

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Iron overload

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Obesity

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Metabolism and nutrition disorders

Tumor lysis syndrome

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Arthralgia

37.9%

25/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

50.0%

22/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Arthritis

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Avascular necrosis

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Back pain

43.9%

29/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

40.9%

18/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Bone pain

27.3%

18/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Buttock pain

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Chest wall pain

12.1%

8/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Generalized muscle weakness

36.4%

24/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Joint range of motion decreased

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Muscle weakness lower limb

19.7%

13/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Muscle weakness upper limb

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Musculoskeletal and connective tissue disorder - Other, specify

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

18.2%

8/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Musculoskeletal deformity

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Myalgia

36.4%

24/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Neck pain

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Osteoporosis

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Musculoskeletal and connective tissue disorders

Pain in extremity

27.3%

18/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Arachnoiditis

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Ataxia

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Central nervous system necrosis

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Cerebrospinal fluid leakage

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Cognitive disturbance

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Depressed level of consciousness

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Dizziness

34.8%

23/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

52.3%

23/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Dysgeusia

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Dysphasia

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Encephalopathy

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Extrapyramidal disorder

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Facial nerve disorder

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Headache

71.2%

47/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

70.5%

31/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Intracranial hemorrhage

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Ischemia cerebrovascular

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Leukoencephalopathy

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Memory impairment

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Nervous system disorders - Other, specify

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

29.5%

13/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Neuralgia

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Nystagmus

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Peripheral motor neuropathy

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Peripheral sensory neuropathy

62.1%

41/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

54.5%

24/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Seizure

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Sinus pain

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Syncope

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Tremor

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Trigeminal nerve disorder

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Nervous system disorders

Vasovagal reaction

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Agitation

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Anxiety

30.3%

20/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

36.4%

16/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Confusion

18.2%

12/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Depression

27.3%

18/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Insomnia

47.0%

31/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

43.2%

19/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Libido decreased

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Personality change

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Psychiatric disorders

Psychosis

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Acute kidney injury

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Hematuria

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Renal and urinary disorders - Other, specify

15.2%

10/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urinary frequency

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urinary incontinence

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urinary retention

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urinary tract obstruction

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urinary tract pain

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Renal and urinary disorders

Urine discoloration

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Breast pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Erectile dysfunction

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Irregular menstruation

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Pelvic pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Reproductive system and breast disorders - Other, specify

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Scrotal pain

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Testicular pain

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Uterine pain

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Vaginal discharge

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Vaginal hemorrhage

6.1%

4/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Reproductive system and breast disorders

Vaginal inflammation

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Allergic rhinitis

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Atelectasis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Bronchopulmonary hemorrhage

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Bronchospasm

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Cough

42.4%

28/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

45.5%

20/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Dyspnea

39.4%

26/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Epistaxis

16.7%

11/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Hiccups

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Hypoxia

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Laryngeal edema

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pharyngeal mucositis

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain

28.8%

19/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pleural effusion

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pleuritic pain

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pneumonitis

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Pneumothorax

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Respiratory, thoracic and mediastinal disorders - Other, specify

28.8%

19/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

31.8%

14/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Sinus disorder

9.1%

6/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Tracheal mucositis

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Respiratory, thoracic and mediastinal disorders

Voice alteration

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Alopecia

37.9%

25/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Dry skin

15.2%

10/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Erythema multiforme

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Hirsutism

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Hyperhidrosis

16.7%

11/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

20.5%

9/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Nail loss

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Pain of skin

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Photosensitivity

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

0.00%

0/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Pruritus

21.2%

14/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

27.3%

12/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Purpura

19.7%

13/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Rash acneiform

16.7%

11/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Rash maculo-papular

39.4%

26/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

40.9%

18/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Scalp pain

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Skin and subcutaneous tissue disorders - Other, specify

33.3%

22/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

34.1%

15/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Skin hyperpigmentation

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Skin hypopigmentation

0.00%

0/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Skin ulceration

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Skin and subcutaneous tissue disorders

Urticaria

4.5%

3/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

6.8%

3/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Flushing

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

11.4%

5/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Hematoma

7.6%

5/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Hot flashes

1.5%

1/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

9.1%

4/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Hypertension

10.6%

7/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

4.5%

2/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Hypotension

19.7%

13/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

13.6%

6/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Phlebitis

3.0%

2/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

2.3%

1/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Thromboembolic event

34.8%

23/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

22.7%

10/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Vascular disorders

Vascular disorders - Other, specify

16.7%

11/66 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

15.9%

7/44 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 287 days (2-974). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.27 years (0.01-11.8). Data is reported for the entire study cohort (n=112) and broken down by arm.

Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Trial Outcomes & Findings for ALL Adult Consortium Trial: Adult ALL Trial (NCT NCT00476190)

Results Overview

Participant Flow

Participant milestones

Reasons for withdrawal

Baseline Characteristics

Baseline characteristics by cohort

PRIMARY outcome

Outcome measures

PRIMARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

SECONDARY outcome

Outcome measures

Adverse Events

Pre-amendment Cohort, 2500 IU/m2 q2 Weeks

Post-amendment Cohort, 2000 IU/m2 q3 Weeks

Serious adverse events

Other adverse events

Additional Information

Dr. Dan DeAngelo

Results disclosure agreements