Trial Outcomes & Findings for Docetaxel, Oxaliplatin, Capecitabine, Fluorouracil, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction (NCT NCT00938470)

NCT ID: NCT00938470

Last Updated: 2018-03-29

Results Overview

Pathologic complete response was defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: Up to 2 years
• Results posted on: 2018-03-29

Participant Flow

Seventy-three participants were enrolled between January 2010 and July 2012.

Seven participants from arm I were enrolled in the early toxicity evaluation portion. Additional sixty-six participants were randomized to arm I or II on the phase II portion of the study. There were 11 cancellations (5 arm I, 6 arm II) and these participants were excluded in all analyses.

Participant milestones

Measure	Arm I (DOC, 5FU/O/RT, Surgery) Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Overall Study COMPLETED	27	25
Overall Study NOT COMPLETED	7	3
Overall Study STARTED	34	28

Reasons for withdrawal

Measure	Arm I (DOC, 5FU/O/RT, Surgery) Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Overall Study Disease Progression	3	0
Overall Study Alternate Treatment	1	0
Overall Study Death	3	2
Overall Study Other Reason	0	1

Baseline Characteristics

Docetaxel, Oxaliplatin, Capecitabine, Fluorouracil, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Esophagus or Gastroesophageal Junction

Baseline characteristics by cohort

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.	Total n=55 Participants Total of all reporting groups
Age, Continuous	62.5 years n=5 Participants	65 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Race/Ethnicity, Customized White	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
ECOG Performance Status 0-1	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Tumor Stage II	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Tumor Stage III	22 Participants n=5 Participants	18 Participants n=7 Participants	40 Participants n=5 Participants
Site of Tumor Esophagus	16 Participants n=5 Participants	11 Participants n=7 Participants	27 Participants n=5 Participants
Site of Tumor Gastroesophageal Junction	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Site of Tumor Gastric Cardia	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Measurable Disease Yes	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Measurable Disease No	17 Participants n=5 Participants	16 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Eligible randomized participants who initiated first cycle of protocol treatment.

Pathologic complete response was defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.

Outcome measures

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Percentage of Participants With Pathologic Complete Response (PCR)	28.6 percentage of participants Interval 13.2 to 48.7	40.7 percentage of participants Interval 22.4 to 61.2

SECONDARY outcome

Timeframe: Up to 2 years

Population: Eligible randomized participants who initiated first cycle of protocol treatment.

Overall survival was defined as the time from randomization to the time of death from any cause. Overall survival was censored at the date of last follow-up visit for patients who are still alive or loss of follow-up.

Outcome measures

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Overall Survival	NA months Interval 24.0 to Median survival and upper limit of 95% CI are not attainable.	18.8 months Interval 13.3 to Upper limit of 95% CI is not attainable.

SECONDARY outcome

Timeframe: Up to 2 years

Population: Eligible randomized participants who initiated first cycle of protocol treatment.

Disease-free survival was defined as the time from randomization to the date of recurrent or death, whichever comes first.

Outcome measures

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Disease-free Survival	31.2 months Interval 15.4 to Upper limit of 95% CI is not attainable.	17.0 months Interval 11.1 to Upper limit of 95% CI is not attainable.

SECONDARY outcome

Timeframe: Up to 2 years

Population: Eligible randomized participants who initiated first cycle of protocol treatment.

Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome measures

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event Grade 3=Severe	10 Participants	12 Participants
Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event Grade 4=Life threatening	10 Participants	7 Participants
Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event Grade 5=Death	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: Eligible randomized participants who initiated first cycle of protocol treatment.

Overall clinical tumor response rate was defined as the percentage of evaluable participants who achieved either complete response (CR) or partial response (PR) noted on the objective status from pre-surgical staging (for arm II) or either from pre-RT or pre-surgical staging (for arm I).> CR was defined as disappearance of all non-target lesion (TL) and normalization of tumor biomarker level, all lymph nodes (LN) must be non-pathological in size (<1 cm short axis); or disappearance of all TL and normalization of tumor biomarkers, any pathological LN (whether target or non-target) must have reduction in short axis to <1 cm; or >=30% decrease in the sum of the diameters of TL taking as reference the baseline sum of the diameters.

Outcome measures

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=28 Participants Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=27 Participants Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Percentage of Participants With Overall Clinical Tumor Response (CR or PR)	32.1 percentage of participants Interval 15.9 to 52.4	33.3 percentage of participants Interval 16.5 to 54.0

Adverse Events

Arm I (DOC, 5FU/O/RT, Surgery)

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Arm II (5FU/O/RT, Surgery)

Serious events: 7 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=34 participants at risk Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=28 participants at risk Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Blood and lymphatic system disorders Disseminated intravascular coagulation	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Cardiac arrest	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Colitis	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Dysphagia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophageal fistula	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophageal pain	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Retroperitoneal hemorrhage	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Sepsis	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Esophageal anastomotic leak	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Lymphocyte count decreased	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Neutrophil count decreased	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Platelet count decreased	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations White blood cell decreased	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Anorexia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hyperglycemia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Death NOS	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.

Other adverse events

Measure	Arm I (DOC, 5FU/O/RT, Surgery) n=34 participants at risk Patients receive 60mg/m\^2 docetaxel (D) IV over 1 hour and 85mg/m\^2 oxaliplatin (O) IV over 2 hours on day 1. Patients also receive 625 mg/m\^2/dose twice a day of capecitabine (C) PO BID on days 1-14. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of the second course, patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. Approximately 4-12 weeks after completion of radiation therapy, patients undergo surgery.	Arm II (5FU/O/RT, Surgery) n=28 participants at risk Patients receive 180 mg/m\^2 per day of fluorouracil (5FU) IV continuously on days 1-5 and 85 mg/m\^2 of oxaliplatin (O) IV over 2 hours on days 1, 15, and 29. Patients also undergo radiation therapy (RT) and then surgery.
Gastrointestinal disorders Esophageal fistula	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophageal pain	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophageal perforation	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophageal stenosis	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Esophagitis	8.8% 3/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	21.4% 6/28 • Number of events 6 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Flatulence	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Dyspepsia	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Dysphagia	76.5% 26/34 • Number of events 68 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	78.6% 22/28 • Number of events 41 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Blood and lymphatic system disorders Anemia	20.6% 7/34 • Number of events 10 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	28.6% 8/28 • Number of events 11 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Blood and lymphatic system disorders Febrile neutropenia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Asystole	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Atrial fibrillation	11.8% 4/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Atrial flutter	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Cardiac arrest	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Heart failure	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Myocardial infarction	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Pericardial effusion	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Pericardial tamponade	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Sinus bradycardia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Supraventricular tachycardia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Ventricular fibrillation	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Cardiac disorders Ventricular tachycardia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Abdominal pain	14.7% 5/34 • Number of events 7 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Colonic obstruction	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Colonic perforation	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Constipation	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Diarrhea	61.8% 21/34 • Number of events 41 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	53.6% 15/28 • Number of events 22 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Dry mouth	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Duodenal fistula	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Gastric fistula	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Gastritis	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Gastroesophageal reflux disease	2.9% 1/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.9% 1/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Gastroparesis	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Ileus	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Mucositis oral	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Nausea	88.2% 30/34 • Number of events 83 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	85.7% 24/28 • Number of events 44 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Oral dysesthesia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Gastrointestinal disorders Vomiting	61.8% 21/34 • Number of events 35 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	64.3% 18/28 • Number of events 32 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Edema limbs	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Edema trunk	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Fatigue	44.1% 15/34 • Number of events 28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	39.3% 11/28 • Number of events 14 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Fever	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Hypothermia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Infusion related reaction	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Multi-organ failure	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Non-cardiac chest pain	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
General disorders Pain	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Abdominal infection	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Bone infection	2.9% 1/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Infections and infestations - Other, specify	2.9% 1/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Lung infection	5.9% 2/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Mucosal infection	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Sepsis	8.8% 3/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Skin infection	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Tooth infection	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Infections and infestations Upper respiratory infection	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Esophageal anastomotic leak	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Gastric anastomotic leak	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Gastrointestinal anastomotic leak	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	2.9% 1/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Intraoperative hemorrhage	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Wound complication	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Injury, poisoning and procedural complications Wound dehiscence	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Alanine aminotransferase increased	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Alkaline phosphatase increased	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Aspartate aminotransferase increased	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Blood bilirubin increased	11.8% 4/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Creatinine increased	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations INR increased	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Lymphocyte count decreased	11.8% 4/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	32.1% 9/28 • Number of events 14 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Neutrophil count decreased	82.4% 28/34 • Number of events 47 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	17.9% 5/28 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Platelet count decreased	64.7% 22/34 • Number of events 66 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	78.6% 22/28 • Number of events 43 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations Weight loss	23.5% 8/34 • Number of events 20 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	28.6% 8/28 • Number of events 12 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Investigations White blood cell decreased	82.4% 28/34 • Number of events 74 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	46.4% 13/28 • Number of events 20 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Anorexia	23.5% 8/34 • Number of events 10 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	39.3% 11/28 • Number of events 12 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Dehydration	20.6% 7/34 • Number of events 9 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	17.9% 5/28 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hyperglycemia	11.8% 4/34 • Number of events 6 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	17.9% 5/28 • Number of events 6 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypernatremia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypoalbuminemia	17.6% 6/34 • Number of events 8 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypocalcemia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypoglycemia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypokalemia	8.8% 3/34 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Metabolism and nutrition disorders Hypophosphatemia	8.8% 3/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Chest wall pain	2.9% 1/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Flank pain	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.8% 4/34 • Number of events 8 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	2.9% 1/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Musculoskeletal and connective tissue disorders Pain in extremity	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Depressed level of consciousness	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Dizziness	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Dysgeusia	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Headache	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Peripheral motor neuropathy	5.9% 2/34 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Peripheral sensory neuropathy	67.6% 23/34 • Number of events 59 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	64.3% 18/28 • Number of events 24 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Nervous system disorders Seizure	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Psychiatric disorders Agitation	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Psychiatric disorders Anxiety	2.9% 1/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Psychiatric disorders Delirium	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Psychiatric disorders Depression	5.9% 2/34 • Number of events 5 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Psychiatric disorders Psychiatric disorders - Other, specify	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Renal and urinary disorders Acute kidney injury	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Renal and urinary disorders Renal and urinary disorders - Other, specify	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Bronchial fistula	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Chylothorax	8.8% 3/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Dyspnea	41.2% 14/34 • Number of events 44 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	46.4% 13/28 • Number of events 19 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	7.1% 2/28 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	10.7% 3/28 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	8.8% 3/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	14.3% 4/28 • Number of events 4 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	5.9% 2/34 • Number of events 3 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Respiratory, thoracic and mediastinal disorders Sore throat	2.9% 1/34 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Alopecia	23.5% 8/34 • Number of events 13 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.9% 1/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/34 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Surgical and medical procedures Surgical and medical procedures - Other, specify	8.8% 3/34 • Number of events 9 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	0.00% 0/28 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Vascular disorders Hypotension	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.
Vascular disorders Thromboembolic event	5.9% 2/34 • Number of events 2 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.	3.6% 1/28 • Number of events 1 • 2 years Adverse events data were reported on 55 eligible randomized participants who initiated first cycle of protocol treatment, 1 ineligible Arm II participant and 6 eligible Arm I participants who enrolled onto the early toxicity evaluation portion of the study.

Additional Information

Steven R Alberts MD MPH

Mayo Clinic

Phone: 507-284-4918

Email: alberts.steven@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60