Trial Outcomes & Findings for Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer (NCT NCT00024102)

NCT ID: NCT00024102

Last Updated: 2016-08-12

Results Overview

Percentage of participants who were alive and relapse-free at time of analysis were counted as "Alive without relapse" at 2.4 years. Participants who had a first local recurrence, first distant metastasis or death from any cause were counted as "relapse, first occurrence". These rates were estimated using the Kaplan Meier method

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 633 participants
• Primary outcome timeframe: randomization until date of first event, or date last known to be event free if no event was reported (up to 5 years)
• Results posted on: 2016-08-12

Participant Flow

This was an intergroup study led by the CALGB. Between September 2001 and December 2006, 633 participants were recruited.

All participants recruited were randomized with equal probability to one of two treatment arms. Randomization was initially stratified by age and performance score. In 2006 tumoral HER2 status was added as a third stratification factor.

Participant milestones

Measure	Standard Chemotherapy Patient/Physician choice of: CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles OR AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles.
Overall Study STARTED	326	307
Overall Study COMPLETED	326	307
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer

Baseline characteristics by cohort

Measure	Standard Chemotherapy n=326 Participants Patient/Physician choice of: CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles OR AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=307 Participants Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles.	Total n=633 Participants Total of all reporting groups
Age, Customized 65-69 years	112 participants n=5 Participants	110 participants n=7 Participants	222 participants n=5 Participants
Age, Customized 70-79 years	200 participants n=5 Participants	183 participants n=7 Participants	383 participants n=5 Participants
Age, Customized >=80 years	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Sex: Female, Male Female	326 Participants n=5 Participants	307 Participants n=7 Participants	633 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	326 participants n=5 Participants	302 participants n=7 Participants	628 participants n=5 Participants
Region of Enrollment Argentina	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Australia	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
ECOG Performance Status 0 or 1 (fully active or minimal symptoms)	317 participants n=5 Participants	295 participants n=7 Participants	612 participants n=5 Participants
ECOG Performance Status 2 (symptoms, but active > 50% of the time)	9 participants n=5 Participants	12 participants n=7 Participants	21 participants n=5 Participants
HER2 Status Negative	246 participants n=5 Participants	232 participants n=7 Participants	478 participants n=5 Participants
HER2 Status Positive	35 participants n=5 Participants	30 participants n=7 Participants	65 participants n=5 Participants
HER2 Status Unknown	45 participants n=5 Participants	45 participants n=7 Participants	90 participants n=5 Participants

PRIMARY outcome

Timeframe: randomization until date of first event, or date last known to be event free if no event was reported (up to 5 years)

Population: RFS used the intent-to-treat approach

Percentage of participants who were alive and relapse-free at time of analysis were counted as "Alive without relapse" at 2.4 years. Participants who had a first local recurrence, first distant metastasis or death from any cause were counted as "relapse, first occurrence". These rates were estimated using the Kaplan Meier method

Outcome measures

Measure	Standard Chemotherapy n=326 Participants Patient/Physician choice of: CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles OR AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=307 Participants Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles.	Capecitabine Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles
Relapse-free Survival Rates at 2.4 Years Relapse, first occurrence	11 percentage of participants	20 percentage of participants	—
Relapse-free Survival Rates at 2.4 Years Alive without relapse	89 percentage of participants	80 percentage of participants	—

SECONDARY outcome

Timeframe: Time from registration to death (up to 15 years)

Population: OS used the intent-to-treat approach.

Percentage of patients who were alive at 2.4 years. This rate was estimated using the Kaplan Meier method.

Outcome measures

Measure	Standard Chemotherapy n=326 Participants Patient/Physician choice of: CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles OR AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=307 Participants Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles.	Capecitabine Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles
Overall Survival Rate at 2.4 Years	93 percentage of participants	88 percentage of participants	—

SECONDARY outcome

Timeframe: Reported during protocol treatment after each cycle

The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity.

Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

Outcome measures

Measure	Standard Chemotherapy n=132 Participants Patient/Physician choice of: CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles OR AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=183 Participants Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles.	Capecitabine n=299 Participants Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles
Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.	92 participants	109 participants	101 participants

Adverse Events

Standard Chemotherapy (CMF)

Serious events: 15 serious events

Other events: 121 other events

Deaths: 0 deaths

Standard Chemotherapy (AC)

Serious events: 17 serious events

Other events: 168 other events

Deaths: 0 deaths

Capecitabine

Serious events: 26 serious events

Other events: 279 other events

Deaths: 0 deaths

Serious adverse events

Measure	Standard Chemotherapy (CMF) n=131 participants at risk CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles	Standard Chemotherapy (AC) n=181 participants at risk AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=299 participants at risk Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Febrile neutropenia	3.8% 5/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Hemoglobin decreased	5.3% 7/131 • Number of events 7 • Reported at the end of each cycle while patients were receiving protocol therapy.	7.2% 13/181 • Number of events 13 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.7% 8/299 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Lymphatics	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Transfusion: pRBCs	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Cardiac disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Edema	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Left ventricular failure	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Myocardial ischemia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Abdominal pain	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Colitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Diarrhea	3.8% 5/131 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.8% 5/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	6.0% 18/299 • Number of events 20 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Esophagitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Gastritis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Mucositis oral	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.8% 5/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Nausea	3.8% 5/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	3.3% 10/299 • Number of events 10 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Typhlitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Vomiting	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.0% 6/299 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Chest pain	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Fatigue	6.1% 8/131 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	5.0% 9/181 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.	5.4% 16/299 • Number of events 20 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Anorectal infection	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection with grade 3 or 4 neutropenia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection without neutropenia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infectious colitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Upper respiratory infection	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Aspartate aminotransferase increased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Coagulopathy	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Creatinine increased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations INR increased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Leukocyte count decreased	9.2% 12/131 • Number of events 13 • Reported at the end of each cycle while patients were receiving protocol therapy.	7.2% 13/181 • Number of events 14 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Lymphocyte count decreased	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Neutrophil count decreased	5.3% 7/131 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	5.5% 10/181 • Number of events 11 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Platelet count decreased	3.1% 4/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	4.4% 8/181 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Anorexia	2.3% 3/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	3.3% 10/299 • Number of events 12 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Blood glucose increased	2.3% 3/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Blood uric acid increased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Dehydration	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.3% 7/299 • Number of events 7 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum albumin decreased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum calcium decreased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum glucose decreased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum magnesium decreased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum potassium decreased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum sodium decreased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Ataxia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Dizziness	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Ischemia cerebrovascular	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Speech disorder	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Syncope	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Rash/Dermatitis BMT	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Reproductive system and breast disorders Vaginal hemorrhage	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.7% 8/299 • Number of events 11 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Rash desquamating	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hypertension	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hypotension	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Peripheral arterial ischemia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Phlebitis	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Thrombosis	2.3% 3/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.

Other adverse events

Measure	Standard Chemotherapy (CMF) n=131 participants at risk CMF: cyclophosphamide (100 mg/m\^2 orally days 1-14)+ MTX (40 mg/m\^2 by IV days 1 and 8) + 5-FU (600 mg/m\^2 by IV days 1 and 8) repeated every 28 days for 6 cycles	Standard Chemotherapy (AC) n=181 participants at risk AC: Cyclophosphamide (600 mg/m\^2 by IV on day 1)+ doxorubicin (60 mg/m\^2 by IV on day 1) repeated every 21 days for 4 cycles	Capecitabine n=299 participants at risk Capecitabine (2000 mg/m\^2 in 2 doses days 1-14) repeated every 21 days for 6 cycles
Blood and lymphatic system disorders Febrile neutropenia	5.3% 7/131 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.	9.9% 18/181 • Number of events 22 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Hemoglobin decreased	41.2% 54/131 • Number of events 158 • Reported at the end of each cycle while patients were receiving protocol therapy.	61.9% 112/181 • Number of events 293 • Reported at the end of each cycle while patients were receiving protocol therapy.	22.4% 67/299 • Number of events 199 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Hemolysis	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Lymphatics	13.0% 17/131 • Number of events 35 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	7.7% 23/299 • Number of events 44 • Reported at the end of each cycle while patients were receiving protocol therapy.
Blood and lymphatic system disorders Transfusion: pRBCs	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Atrial fibrillation	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Cardiac disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Edema	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.3% 7/299 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Myocardial ischemia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Cardiac disorders Sinus tachycardia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Cataract	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Conjunctivitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Diplopia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Flashing vision	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Retinal detachment	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Vision blurred	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Eye disorders Watering eyes	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Abdominal pain	3.1% 4/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Colitis	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Constipation	2.3% 3/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 10 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Diarrhea	44.3% 58/131 • Number of events 108 • Reported at the end of each cycle while patients were receiving protocol therapy.	17.7% 32/181 • Number of events 52 • Reported at the end of each cycle while patients were receiving protocol therapy.	46.2% 138/299 • Number of events 276 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Dry mouth	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Dyspepsia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Gastritis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Gastrointestinal disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Hemorrhoids	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Mucositis oral	29.0% 38/131 • Number of events 61 • Reported at the end of each cycle while patients were receiving protocol therapy.	32.0% 58/181 • Number of events 89 • Reported at the end of each cycle while patients were receiving protocol therapy.	23.7% 71/299 • Number of events 117 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Nausea	50.4% 66/131 • Number of events 151 • Reported at the end of each cycle while patients were receiving protocol therapy.	58.0% 105/181 • Number of events 201 • Reported at the end of each cycle while patients were receiving protocol therapy.	34.1% 102/299 • Number of events 185 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Rectal pain	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Typhlitis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Gastrointestinal disorders Vomiting	22.1% 29/131 • Number of events 40 • Reported at the end of each cycle while patients were receiving protocol therapy.	22.1% 40/181 • Number of events 48 • Reported at the end of each cycle while patients were receiving protocol therapy.	9.7% 29/299 • Number of events 34 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Chest pain	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Fatigue	65.6% 86/131 • Number of events 299 • Reported at the end of each cycle while patients were receiving protocol therapy.	71.3% 129/181 • Number of events 321 • Reported at the end of each cycle while patients were receiving protocol therapy.	54.2% 162/299 • Number of events 504 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Fever	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Gait abnormal	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders General symptom	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Injection site reaction	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
General disorders Pain	3.1% 4/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Hepatobiliary disorders Hepatobiliary disease	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Biliary tract infection	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Catheter related infection	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection with grade 3 or 4 neutropenia	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.8% 5/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection with unknown ANC	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Infection without neutropenia	3.8% 5/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Pneumonia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Sepsis	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Skin infection	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Infections and infestations Urinary tract infection	0.76% 1/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Injury, poisoning and procedural complications Bruising	1.5% 2/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Injury, poisoning and procedural complications Vascular access complication	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Alanine aminotransferase increased	2.3% 3/131 • Number of events 7 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Alkaline phosphatase	0.76% 1/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Alkaline phosphatase increased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Aspartate aminotransferase increased	3.1% 4/131 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Blood bilirubin increased	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Creatinine increased	7.6% 10/131 • Number of events 14 • Reported at the end of each cycle while patients were receiving protocol therapy.	3.3% 6/181 • Number of events 10 • Reported at the end of each cycle while patients were receiving protocol therapy.	7.4% 22/299 • Number of events 46 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Gamma-glutamyltransferase increased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations INR increased	3.1% 4/131 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 11 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Laboratory test abnormal	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Leukocyte count decreased	66.4% 87/131 • Number of events 256 • Reported at the end of each cycle while patients were receiving protocol therapy.	61.9% 112/181 • Number of events 270 • Reported at the end of each cycle while patients were receiving protocol therapy.	10.4% 31/299 • Number of events 71 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Lymphocyte count decreased	4.6% 6/131 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Neutrophil count decreased	28.2% 37/131 • Number of events 66 • Reported at the end of each cycle while patients were receiving protocol therapy.	29.8% 54/181 • Number of events 106 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Neutrophils/granulocytes (ANC/AGC) for BMT studies, if specified in the protocol.	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Platelet count decreased	35.1% 46/131 • Number of events 105 • Reported at the end of each cycle while patients were receiving protocol therapy.	26.0% 47/181 • Number of events 83 • Reported at the end of each cycle while patients were receiving protocol therapy.	3.7% 11/299 • Number of events 13 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Platelets for BMT studies, if specified in the protocol.	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Investigations Weight loss	1.5% 2/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Anorexia	27.5% 36/131 • Number of events 64 • Reported at the end of each cycle while patients were receiving protocol therapy.	22.7% 41/181 • Number of events 67 • Reported at the end of each cycle while patients were receiving protocol therapy.	17.4% 52/299 • Number of events 92 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Blood glucose increased	7.6% 10/131 • Number of events 25 • Reported at the end of each cycle while patients were receiving protocol therapy.	5.5% 10/181 • Number of events 16 • Reported at the end of each cycle while patients were receiving protocol therapy.	4.0% 12/299 • Number of events 23 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Blood uric acid increased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Dehydration	3.1% 4/131 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum albumin decreased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum calcium decreased	2.3% 3/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum glucose decreased	0.76% 1/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum phosphate decreased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum potassium decreased	1.5% 2/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 3/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.0% 6/299 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum potassium increased	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum sodium decreased	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.
Metabolism and nutrition disorders Serum sodium increased	2.3% 3/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Back pain	1.5% 2/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Bone pain	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Musculoskeletal disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Musculoskeletal and connective tissue disorders Myalgia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplasia	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Ataxia	1.5% 2/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Depressed level of consciousness	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Dizziness	3.1% 4/131 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Dysgeusia	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 7 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Headache	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.7% 5/299 • Number of events 9 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Intracranial hemorrhage	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Ischemia cerebrovascular	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Neurological disorder NOS	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Peripheral motor neuropathy	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Peripheral sensory neuropathy	2.3% 3/131 • Number of events 4 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.0% 6/299 • Number of events 10 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Sense of smell	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Speech disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Nervous system disorders Syncope	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Psychiatric disorders Agitation	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Psychiatric disorders Anxiety	0.76% 1/131 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Psychiatric disorders Confusion	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Psychiatric disorders Depression	1.5% 2/131 • Number of events 7 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Psychiatric disorders Insomnia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Renal and urinary disorders Urogenital disorder	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Reproductive system and breast disorders Pelvic pain	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Reproductive system and breast disorders Vaginal inflammation	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.76% 1/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.67% 2/299 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 3 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	2.3% 3/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.2% 4/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Respiratory, thoracic and mediastinal disorders Respiratory disorder	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Alopecia	4.6% 6/131 • Number of events 10 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.8% 5/181 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Hand-and-foot syndrome	6.1% 8/131 • Number of events 15 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.1% 2/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	70.2% 210/299 • Number of events 657 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Pigmentation changes (e.g., vitiligo)	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.0% 3/299 • Number of events 8 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Pruritus	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Rash desquamating	9.9% 13/131 • Number of events 20 • Reported at the end of each cycle while patients were receiving protocol therapy.	8.3% 15/181 • Number of events 25 • Reported at the end of each cycle while patients were receiving protocol therapy.	18.4% 55/299 • Number of events 109 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Skin disorder	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Skin and subcutaneous tissue disorders Sweating	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Flushing	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hemorrhage	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/299 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hot flashes	0.00% 0/131 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hypertension	0.76% 1/131 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.00% 0/181 • Reported at the end of each cycle while patients were receiving protocol therapy.	1.3% 4/299 • Number of events 6 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Hypotension	1.5% 2/131 • Number of events 2 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.55% 1/181 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.
Vascular disorders Thrombosis	3.8% 5/131 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	2.8% 5/181 • Number of events 5 • Reported at the end of each cycle while patients were receiving protocol therapy.	0.33% 1/299 • Number of events 1 • Reported at the end of each cycle while patients were receiving protocol therapy.

Additional Information

Hyman Muss, MD

University of North Carolina

Email: hyman.muss@gmail.com

Results disclosure agreements

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