Trial Outcomes & Findings for A Study in Adults With Untreated Acute Lymphoblastic Leukemia (NCT NCT00136435)

Last Updated: 2025-10-20

Results Overview

Feasibility based on the rate of asparaginase completion defined as the percentage of patients who, after having achieved a complete remission after induction therapy, complete all 30 doses of asparaginase as part of intensification therapy. Complete remission is defined as peripheral blood without lymphoblasts, a bone marrow with \<5% lymphoblasts, an antigen-presenting cell (APC) \> 1000/mm3, platelets \> 100,000/mm3, and no evidence of extramedullary leukemia.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.

Results posted on

2025-10-20

Participant Flow

Participant milestones

Participant milestones
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Overall Study STARTED	100
Overall Study Started Study Treatment	98
Overall Study Eligible and Treated	92
Overall Study Achieved Complete Remission	78
Overall Study Initiated Asparaginase Consolidation Therapy	57
Overall Study COMPLETED	36
Overall Study NOT COMPLETED	64

Reasons for withdrawal

Reasons for withdrawal
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Overall Study Ineligible	8
Overall Study Induction Death	1
Overall Study Induction Failure	10
Overall Study Withdrew prior to initiating imatinib/Ph+	3
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	19
Overall Study Relapse	4
Overall Study Transplant in first Complete Remission (CR)	16

Baseline Characteristics

A Study in Adults With Untreated Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=100 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Age, Customized 18-29 years	49 Participants n=5 Participants
Age, Customized 30-50 years	51 Participants n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	88 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Immunophenotype B-cell	81 Participants n=5 Participants
Immunophenotype T-cell	19 Participants n=5 Participants
White Blood Count (WBC) (x 10^-3) at diagnosis < 20	60 Participants n=5 Participants
White Blood Count (WBC) (x 10^-3) at diagnosis >/= 20	39 Participants n=5 Participants
White Blood Count (WBC) (x 10^-3) at diagnosis Unknown	1 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 1 (-) CSF WBC <5 without blasts	83 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 2 (+) CSF WBC <5 with blasts	6 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis CNS 3 (+) CSF WBC >=5 with blasts	1 Participants n=5 Participants
Central Nervous System (CNS) status at diagnosis Unknown	10 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Risk classification Standard Risk (SR)	42 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Risk classification High Risk (HR)	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at the end of the 30-week post-induction treatment period or when the participant comes off treatment, whichever occurs first.

Population: The analysis dataset is comprised of all patients who initiated asparaginase consolidation therapy.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=57 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Asparaginase Completion Rate	63 Percentage of patients Interval 54.0 to 72.0

SECONDARY outcome

Timeframe: Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment, (up to 5 years). Relevant for this measure is 4 years from the date of complete remission.

Population: The analysis dataset is comprised of all eligible patients who achieved a CR.

Disease-Free Survival (DFS) based on the Kaplan-Meier method is defined as the time from achieving a complete remission to the first of disease recurrence or death, censored at time of last disease assessment. 4-year DFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from complete remission. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, fluorescent in situ hybridization (FISH), immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the cerebrospinal fluid (CSF) may qualify as CNS leukemia) also qualifies if confirmed by the PI.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=78 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
4-year Disease-Free Survival	69 Percent probability Interval 56.0 to 78.0

SECONDARY outcome

Timeframe: Assessed continuously throughout the treatment period, and annually for 5 years following the completion of protocol treatment (unless the participant dies or is lost to follow-up). Median follow-up for the whole trial is 4.5 years (95% CI:4.1-5.0 years).

Population: The analysis dataset is comprised of all eligible patients.

Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from study entry to death from any cause, and will be censored the date last known alive. 4-year OS is the percent probability of patients remaining alive 4 years from study entry.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=92 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
4-year Overall Survival	67 Percent probability Interval 56.0 to 76.0

SECONDARY outcome

Population: The analysis dataset is comprised of all eligible patients.

Event-Free Survival (EFS) based on the Kaplan-Meier method is defined as the time from study entry to the first event of death during induction therapy, failure to achieve CR at the end of induction, death during remission, or relapse. 4-year EFS is the percent probability of patients remaining alive, relapse-free and without occurrence of second malignant neoplasm 4 years from study entry. Patients not achieving a CR will be considered events at time zero. EFS will be censored at time of last disease assessment. Disease relapse is defined as \>25% lymphoblasts identified morphologically in bone marrow aspirate/biopsy, or identification of lymphoblasts in marrow (any percentage) identified to be leukemic by flow cytometry, cytogenetics, FISH, immunohistochemistry, or other tests. Appearance of leukemic cells at any extramedullary site (a single, unequivocal lymphoblast in the CSF may qualify as CNS leukemia) also qualifies if confirmed by the PI.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=92 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
4-year Event-Free Survival	58 Percent probability Interval 47.0 to 68.0

SECONDARY outcome

Timeframe: Samples for nadir serum asparaginase activity levels were assayed prior to asparaginase dose given during post-induction, at Weeks 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, and 30.

Population: The analysis dataset is comprised of all eligible patients for whom serum asparaginase activity levels were assayed.

Nadir serum asparaginase activity (NSAA) levels were estimated based on established methods.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=92 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Post-Induction Nadir Serum Asparaginase Activity Level Week 2 NSAA Level	0 IU/ml Interval 0.0 to 0.172
Post-Induction Nadir Serum Asparaginase Activity Level Week 4 NSAA Level	0.047 IU/ml Interval 0.0 to 0.318
Post-Induction Nadir Serum Asparaginase Activity Level Week 7 NSAA Level	0.0825 IU/ml Interval 0.0 to 0.661
Post-Induction Nadir Serum Asparaginase Activity Level Week 10 NSAA Level	0.088 IU/ml Interval 0.0 to 0.353
Post-Induction Nadir Serum Asparaginase Activity Level Week 13 NSAA Level	0.118 IU/ml Interval 0.0 to 0.315
Post-Induction Nadir Serum Asparaginase Activity Level Week 16 NSAA Level	0.069 IU/ml Interval 0.0 to 0.259
Post-Induction Nadir Serum Asparaginase Activity Level Week 19 NSAA Level	0.075 IU/ml Interval 0.0 to 0.248
Post-Induction Nadir Serum Asparaginase Activity Level Week 22 NSAA Level	0.0865 IU/ml Interval 0.0 to 0.443
Post-Induction Nadir Serum Asparaginase Activity Level Week 25 NSAA Level	0.0925 IU/ml Interval 0.0 to 0.236
Post-Induction Nadir Serum Asparaginase Activity Level Week 28 NSAA Level	0.072 IU/ml Interval 0.0 to 0.255
Post-Induction Nadir Serum Asparaginase Activity Level Week 30 NSAA Level	0.065 IU/ml Interval 0.0 to 0.249

SECONDARY outcome

Timeframe: Assessed on an ongoing basis (at least once every 3 months) while patient is on study, and including the treatment phases of Induction, CNS, Intensification, and Continuation. Treatment duration for this study was a median (range) of 507 days (0-1097).

Population: The analysis dataset is comprised of all eligible patients.

Asparaginase-related toxicity rate is defined as the percentage of patients who experience allergy (all grades), pancreatitis, thrombotic or bleeding complications, bone fracture, or avascular necrosis based on Common Terminology Criteria for Adverse Events (CTCAE) v2.

Outcome measures

Outcome measures
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=92 Participants prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Number of Participants With Asparaginase-Related Toxicity Overall Number of Participants with Pancreatitis	10 participants
Number of Participants With Asparaginase-Related Toxicity Overall Number of Participants with Allergy/rash	5 participants
Number of Participants With Asparaginase-Related Toxicity Overall Number of Participants with Thrombosis/embolism	16 participants
Number of Participants With Asparaginase-Related Toxicity Overall Number of Participants with Bone fracture	7 participants
Number of Participants With Asparaginase-Related Toxicity Overall Number of Participants with Avascular necrosis	5 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Pancreatitis in Induction	1 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Allergy/rash in Induction	1 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Thrombosis/embolism in Induction	1 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Bone fracture in Induction	0 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Avascular necrosis in Induction	0 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Pancreatitis in Intensification	8 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Allergy/rash in Intensification	4 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Thrombosis/embolism in Intensification	14 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Bone fracture in Intensification	3 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Avascular necrosis in Intensification	2 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Pancreatitis in Continuation	2 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Allergy/rash in Continuation	0 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Thrombosis/embolism in Continuation	2 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Bone fracture in Continuation	5 participants
Number of Participants With Asparaginase-Related Toxicity Number of Participants with Avascular necrosis in Continuation	4 participants

Adverse Events

Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase

Serious events: 98 serious events

Other events: 0 other events

Deaths: 40 deaths

Serious adverse events

Serious adverse events
Measure	Induction, CNS, and Intensification With Pharmacokinetically Individualized Doses of L-asparaginase n=98 participants at risk prednisone: Induction Phase: Orally days 1-28 doxorubicin: Induction Phase: Intravenously days 1 and 2 CNS Therapy: Intravenously day 1 Intensification: Given day 1 of each cycle vincristine: Induction: Intravenously days 1, 8, 15, and 22. If complete remission not achieved, will be given on days 29, 36 and 43. CNS Therapy: Intravenously day 1. Intensification: Intravenously day 1 of each cycle. Continuation: Intravenously day 1 of each cycle methotrexate: Induction: Intravenously day 3. CNS Therapy: Intrathecally 4x over two weeks Intensification: Intrathecally every 18 weeks Continuation: Intravenously weekly and intrathecally every 18 weeks asparaginase: Induction: Given into the muscle on day 5 dexamethasone: Intensification: Orally days 1-5 of each cycle cranial radiation: 10 daily treatments during CNS phase leucovorin: Induction: Intravenously/orally 36 hours after methotrexate cytarabine: Induction: Intrathecally days 1, 15, 29 CNS Therapy: Intrathecally 4x over 2 weeks Intensification: Intrathecally every 18 weeks Continuation: Intrathecally every 18 weeks hydrocortisone: Induction: Intrathecally days 15 and 29. Intensification: Intrathecally every 18 weeks. Continuation: Intrathecally every 18 weeks. 6-mercaptopurine (6-MP): CNS Therapy: Orally days 1-14. Intensification: Orally on days 1-14. Continuation: Orally on days 1-14. e. coli L-asparaginase: Intensification: Given in to the muscle weekly.
Blood and lymphatic system disorders Anemia	95.9% 94/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	18.4% 18/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	30.6% 30/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	57.1% 56/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 tachycardia	22.4% 22/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	9.2% 9/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	22.4% 22/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	11.2% 11/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Conjunctivitis	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	10.2% 10/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Glaucoma	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Night blindness	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	56.1% 55/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Ascites	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	52.0% 51/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	66.3% 65/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	32.7% 32/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	35.7% 35/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Dysphasia	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	10.2% 10/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 hemorrhage	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	41.8% 41/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Ileus	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	72.4% 71/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	84.7% 83/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	11.2% 11/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	20.4% 20/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	77.6% 76/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	24.5% 24/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	83.7% 82/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	27.6% 27/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	15.3% 15/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	9.2% 9/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	19.4% 19/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	67.3% 66/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	10.2% 10/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Anaphylaxis	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	75.5% 74/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	15.3% 15/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	18.4% 18/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	91.8% 90/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	19.4% 19/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	90.8% 89/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	73.5% 72/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 T increased	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	16.3% 16/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	30.6% 30/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	75.5% 74/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	16.3% 16/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	9.2% 9/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	95.9% 94/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	92.9% 91/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	9.2% 9/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	23.5% 23/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Alkalosis	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	71.4% 70/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	20.4% 20/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	84.7% 83/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	14.3% 14/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	19.4% 19/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	30.6% 30/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	27.6% 27/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	21.4% 21/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	26.5% 26/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	25.5% 25/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	21.4% 21/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	35.7% 35/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	30.6% 30/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	26.5% 26/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	36.7% 36/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	50.0% 49/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Myositis	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	14.3% 14/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	49.0% 48/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	19.4% 19/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	76.5% 75/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	22.4% 22/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	16.3% 16/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	67.3% 66/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	37.8% 37/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	42.9% 42/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Euphoria	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	56.1% 55/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Proteinuria	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	10.2% 10/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	11.2% 11/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 dryness	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Apnea	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	53.1% 52/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	31.6% 31/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	24.5% 24/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	36.7% 36/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	55.1% 54/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	12.2% 12/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	30.6% 30/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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 Palmar-plantar erythrodysesthesia syndrome	2.0% 2/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	1.0% 1/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	26.5% 26/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	48.0% 47/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	49.0% 48/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	5.1% 5/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	4.1% 4/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	7.1% 7/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	8.2% 8/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	6.1% 6/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	17.3% 17/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	3.1% 3/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	25.5% 25/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and 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	20.4% 20/98 • Adverse events (AE) were continuously monitored and reported every 3 months during treatment. Adverse events were monitored for the treatment duration of this study, which was a median (range) of 507 days (0-1097). All-Cause Mortality was monitored for the duration of follow-up for this study, which was a median (range) of 3.2 (0-7.9) years. Data is reported for the entire study cohort. Reporting included all observed adverse events, with grade and attribution to study treatment. Maximum grade by type was calculated with serious adverse events defined as either 1) G5, 2) G4 unless myelosuppression or unequivocally due to disease or considered expected for chemotherapy drugs used, 3) G2 or G3 events that are unexpected and Possibly, Probably, or Definitely related to study treatment. Since SAE data was not collected separately, all AEs have been reported in the SAE table.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Dan DeAngelo

Dana Farber Cancer Institute

Phone: 617-582-8410

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place