Trial Outcomes & Findings for S0124: Cisplatin Combined With Irinotecan or Etoposide For Extensive-Stage Small Cell Lung Cancer (NCT NCT00045162)

NCT ID: NCT00045162

Last Updated: 2018-07-31

Results Overview

Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 671 participants
• Primary outcome timeframe: Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment.
• Results posted on: 2018-07-31

Participant Flow

Participant milestones

Measure	Cisplatin + Irinotecan	Cisplatin + Etoposide
Overall Study STARTED	336	335
Overall Study COMPLETED	194	217
Overall Study NOT COMPLETED	142	118

Reasons for withdrawal

Measure	Cisplatin + Irinotecan	Cisplatin + Etoposide
Overall Study Ineligible	12	8
Overall Study Not treated	7	2
Overall Study Adverse Event	55	50
Overall Study Lack of Efficacy	32	29
Overall Study Death	10	10
Overall Study Withdrawal by Subject	5	3
Overall Study Other	21	16

Baseline Characteristics

S0124: Cisplatin Combined With Irinotecan or Etoposide For Extensive-Stage Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Cisplatin + Irinotecan n=324 Participants	Cisplatin + Etoposide n=327 Participants	Total n=651 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	136 Participants n=5 Participants	145 Participants n=7 Participants	281 Participants n=5 Participants
Sex: Female, Male Male	188 Participants n=5 Participants	182 Participants n=7 Participants	370 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	289 Participants n=5 Participants	288 Participants n=7 Participants	577 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	28 Participants n=5 Participants	32 Participants n=7 Participants	60 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 particpants n=5 Participants	0 particpants n=7 Participants	2 particpants n=5 Participants
Race/Ethnicity, Customized Asian	4 particpants n=5 Participants	1 particpants n=7 Participants	5 particpants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 particpants n=5 Participants	0 particpants n=7 Participants	0 particpants n=5 Participants
Race/Ethnicity, Customized Black or African American	14 particpants n=5 Participants	18 particpants n=7 Participants	32 particpants n=5 Participants
Race/Ethnicity, Customized White	300 particpants n=5 Participants	304 particpants n=7 Participants	604 particpants n=5 Participants
Race/Ethnicity, Customized More than one race	2 particpants n=5 Participants	0 particpants n=7 Participants	2 particpants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 particpants n=5 Participants	4 particpants n=7 Participants	6 particpants n=5 Participants

PRIMARY outcome

Timeframe: Weekly while on treatment, then every 3 months for first year, then every 6 months unitl a maximum of 3 years from enrollment.

Overall survival was defined as the duration between the date of randomization( enrollment) and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.

Outcome measures

Measure	Cisplatin + Irinotecan n=324 Participants	Cisplatin + Etoposide n=327 Participants
Overall Survival	9.9 Months Interval 9.2 to 11.1	9.1 Months Interval 8.4 to 9.9

SECONDARY outcome

Timeframe: Every 6 weeks until disease progression or a maximum of 3 years from the date of enrollment.

Progression-Free Survival was defined as the duration from the date of randomization (enrollment) until the date of documentation of progression as defined by RECIST (a 20% increase over nadir in the sum of longest diameters of target lesions, clear progression of a non-target lesion in the opinion of the treating investigator, appearance of new lesions, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and without evidence of progression were censored at the date of last contact.

Outcome measures

Measure	Cisplatin + Irinotecan n=324 Participants	Cisplatin + Etoposide n=327 Participants
Progression-free Survival	5.7 months Interval 5.1 to 6.1	5.2 months Interval 4.9 to 5.5

SECONDARY outcome

Timeframe: Every 6 weeks while on protocol treatment for a maximum of 12 weeks

Patients underwent chest CT/MRI every 6 weeks while on treatment and tumor response was evaluated by RECIST in the subset of patients with at least one target lesion at baseline. A target lesion was defined as a lesion with a longest diameter of at least 2 cm ( or at least 1 cm if by spiral CT). A complete response (CR) was defined as the disappearance of all disease, including non-target lesions. A partial response (PR) was defined as a 30% or greater decrease in the sum of the longest diameters. Confirmation of a CR or PR was defined as a second determination of CR or PR at least 4 weeks after the first determination.

Outcome measures

Measure	Cisplatin + Irinotecan n=324 Participants	Cisplatin + Etoposide n=327 Participants
Confirmed and Unconfirmed Complete and Partial Responses.	197 participants	190 participants

SECONDARY outcome

Timeframe: Every 4 weeks while subject on protocol treatment for a maximum of 12 weeks.

Population: Eligible patients who received protocol treatment.

Only adverse events that are possibly, probably or definitely related to study drug are reported. Only patients who received protocol treatment and were assessed for adverse events are included.

Outcome measures

Measure	Cisplatin + Irinotecan n=321 Participants	Cisplatin + Etoposide n=327 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Pneumothorax	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Prothrombin time increase	3 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Vomiting	34 Participants	30 Participants
Number of Patients With a Given Type and Grade of Adverse Event. ARDS	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Abdominal pain/cramping	8 Participants	8 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Acidosis	2 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Alkaline phosphatase increase	2 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Allergic reaction	0 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Anal incontinence	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Anemia	19 Participants	40 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Anorexia	36 Participants	17 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Anxiety/agitation	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Apnea	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Arrhythmia, NOS	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Arthralgia	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Ataxia (incoordination)	1 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Bilirubin increase	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Blurred vision	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Bone pain	8 Participants	6 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Cardiac ischemia/infarction	1 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Cardiovascular-other	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Cataract	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Cerebrovascular ischemia	1 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Chest pain,not cardio or pleur	4 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Colitis	2 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Confusion	3 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Constipation/bowel obstruction	4 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Creatinine increase	9 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Dehydration	54 Participants	27 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Delusions	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Depression	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Diarrhea without colostomy	61 Participants	9 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Dizziness/light headedness	2 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Dyspepsia/heartburn	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Dyspnea	27 Participants	21 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Edema	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Epistaxis	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Erythema multiforme/blistering	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Esophagitis/dysphagia	2 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Fatigue/malaise/lethargy	45 Participants	35 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Febrile neutropenia	11 Participants	33 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Fever without neutropenia	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Flu-like symptoms-other	2 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. GGT increase	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. GI Mucositis, NOS	0 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. GI-other	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. GU-other	2 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Gastric ulcer	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Gastritis	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Headache	2 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hematemesis	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hematologic-other	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hemorrhage-other	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hyperglycemia	12 Participants	17 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hyperkalemia	3 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypermagnesemia	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypernatremia	1 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypertension	2 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hyperuricemia	1 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypoalbuminemia	2 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypocalcemia	6 Participants	8 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypoglycemia	2 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypokalemia	19 Participants	21 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypomagnesemia	3 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hyponatremia	38 Participants	28 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypophosphatemia	7 Participants	5 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypotension	14 Participants	8 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Hypoxia	7 Participants	6 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Ileus	2 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Infection w/o 3-4 neutropenia	12 Participants	13 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Infection with 3-4 neutropenia	20 Participants	24 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Infection, unk ANC	2 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Inner ear-hearing loss	1 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Insomnia	1 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Joint,muscle,bone-other	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. LVEF decrease/CHF	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Leukopenia	57 Participants	109 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Lipase increase	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Lung-other	0 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Lymphopenia	8 Participants	9 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Melena/ GI bleeding	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Metabolic-other	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Mood/consciousness change, NOS	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Muscle weakness (not neuro)	4 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Myalgia	1 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Nausea	46 Participants	35 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Neuro-other	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Neutropenia/granulocytopenia	108 Participants	224 Participants
Number of Patients With a Given Type and Grade of Adverse Event. PRBC transfusion	36 Participants	62 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Pain-other	3 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Personality/behavioral change	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Platelet transfusion	1 Participants	13 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Pneumonitis/infiltrates	4 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Pruritus	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. RT-pain	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Rash/desquamation	0 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Renal failure	4 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Reportable adverse event, NOS	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Respiratory infect w/ neutrop	3 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Respiratory infect w/o neutrop	3 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Respiratory infection, unk ANC	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. SGOT (AST) increase	3 Participants	4 Participants
Number of Patients With a Given Type and Grade of Adverse Event. SGPT (ALT) increase	3 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. SIADH	2 Participants	3 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Second primary	2 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Seizures	2 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Sensory neuropathy	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Sinus tachycardia	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Somnolence/consciousness loss	2 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Stomatitis/pharyngitis	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Supraventricular arrhythmia	3 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Syncope	5 Participants	7 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Thrombocytopenia	13 Participants	52 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Thrombosis/embolism	8 Participants	15 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Thrombotic microangiopathy	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Tumor lysis syndrome	2 Participants	2 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Ureteral obstruction	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Urinary electrolyte wasting	0 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Urinary retention	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Urinary tr infect w/ neutrop	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Ventricular arrhythmia	1 Participants	1 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Voice change/stridor/larynx	2 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Weakness (motor neuropathy)	1 Participants	0 Participants
Number of Patients With a Given Type and Grade of Adverse Event. Weight loss	3 Participants	1 Participants

Adverse Events

Cisplatin + Irinotecan

Serious events: 107 serious events

Other events: 314 other events

Deaths: 0 deaths

Cisplatin + Etoposide

Serious events: 31 serious events

Other events: 317 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cisplatin + Irinotecan n=321 participants at risk	Cisplatin + Etoposide n=327 participants at risk
Blood and lymphatic system disorders Anemia	0.93% 3/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders Febrile neutropenia	1.6% 5/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders PRBC transfusion	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders Platelet transfusion	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders Thrombotic microangiopathy	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Cardiac disorders Cardiac ischemia/infarction	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Cardiac disorders Cardiovascular-other	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Cardiac disorders LVEF decrease/CHF	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Cardiac disorders Supraventricular arrhythmia	1.2% 4/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Cardiac disorders Ventricular arrhythmia	0.93% 3/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Abdominal pain/cramping	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Colitis	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Constipation/bowel obstruction	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Diarrhea without colostomy	9.0% 29/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Gastritis	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Nausea	2.5% 8/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Rectal bleeding/hematochezia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Stomatitis/pharyngitis	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Vomiting	4.0% 13/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Edema	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Fatigue/malaise/lethargy	3.4% 11/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Flu-like symptoms-other	3.4% 11/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	1.8% 6/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Pain-other	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Reportable adverse event, NOS	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	1.2% 4/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Infection w/o 3-4 neutropenia	1.9% 6/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Infection with 3-4 neutropenia	2.5% 8/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	1.8% 6/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Infection, unk ANC	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Respiratory infect w/ neutrop	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Respiratory infect w/o neutrop	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Respiratory infection, unk ANC	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Urinary tr infect w/ neutrop	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Abnormal troponin I (cTnI)	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Amylase increase	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations CPK increase	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Creatinine increase	2.8% 9/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Leukopenia	1.6% 5/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Lipase increase	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Neutropenia/granulocytopenia	5.9% 19/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Prothrombin time increase	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations SIADH	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Thrombocytopenia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Weight loss	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Anorexia	2.2% 7/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Dehydration	10.3% 33/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperglycemia	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperkalemia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypernatremia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypocalcemia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypoglycemia	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypokalemia	1.6% 5/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyponatremia	3.4% 11/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypophosphatemia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Tumor lysis syndrome	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Bone pain	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Chest pain,not cardio or pleur	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Joint,muscle,bone-other	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness (not neuro)	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Myalgia/arthralgia, NOS	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second primary	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Ataxia (incoordination)	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders CNS hemorrhage	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Cerebrovascular ischemia	0.93% 3/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Dizziness/vertigo, NOS	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Headache	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Neuropathic pain	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Seizures	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Syncope	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Weakness (motor neuropathy)	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Anxiety/agitation	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Confusion	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Depression	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Hallucinations	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Mood/consciousness change, NOS	0.62% 2/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Personality/behavioral change	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Renal and urinary disorders Renal failure	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Renal and urinary disorders Urinary electrolyte wasting	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Reproductive system and breast disorders Pelvic pain	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders ARDS	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.5% 8/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.92% 3/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.6% 5/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Pneumonitis/infiltrates	0.93% 3/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.31% 1/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Vascular disorders Hypotension	2.8% 9/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Vascular disorders Peripheral arterial ischemia	0.31% 1/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Vascular disorders Thrombosis/embolism	3.1% 10/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.61% 2/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.

Other adverse events

Measure	Cisplatin + Irinotecan n=321 participants at risk	Cisplatin + Etoposide n=327 participants at risk
Blood and lymphatic system disorders Anemia	66.7% 214/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	73.4% 240/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	10.4% 34/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Blood and lymphatic system disorders PRBC transfusion	10.9% 35/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	19.0% 62/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Ear and labyrinth disorders Ear-other	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	5.5% 18/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Ear and labyrinth disorders Inner ear-hearing loss	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	9.2% 30/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Abdominal pain/cramping	19.9% 64/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	13.8% 45/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Constipation/bowel obstruction	22.7% 73/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	30.3% 99/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Diarrhea without colostomy	56.7% 182/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	26.0% 85/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Dyspepsia/heartburn	5.6% 18/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	8.0% 26/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Nausea	67.0% 215/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	69.7% 228/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Stomatitis/pharyngitis	9.7% 31/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	11.6% 38/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Gastrointestinal disorders Vomiting	41.1% 132/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	43.4% 142/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Edema	15.9% 51/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	16.2% 53/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Fatigue/malaise/lethargy	72.6% 233/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	75.2% 246/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
General disorders Pain-other	10.0% 32/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	14.1% 46/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Infection w/o 3-4 neutropenia	13.4% 43/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	13.1% 43/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Infections and infestations Infection with 3-4 neutropenia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	5.5% 18/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Alkaline phosphatase increase	15.6% 50/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	18.0% 59/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Creatinine increase	14.0% 45/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	20.2% 66/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Leukopenia	50.5% 162/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	63.6% 208/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Lymphopenia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	7.0% 23/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Neutropenia/granulocytopenia	54.5% 175/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	78.0% 255/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations SGOT (AST) increase	12.8% 41/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	10.7% 35/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations SGPT (ALT) increase	12.5% 40/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	11.3% 37/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Thrombocytopenia	24.6% 79/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	51.1% 167/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Investigations Weight loss	30.5% 98/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	26.0% 85/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Anorexia	41.4% 133/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	40.7% 133/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Dehydration	23.7% 76/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	21.7% 71/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperglycemia	27.1% 87/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	23.9% 78/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperkalemia	5.3% 17/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	15.9% 51/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	18.3% 60/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypocalcemia	17.1% 55/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	18.3% 60/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	5.2% 17/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypokalemia	15.3% 49/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	15.3% 50/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hypomagnesemia	13.4% 43/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	14.4% 47/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyponatremia	21.2% 68/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	22.0% 72/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Bone pain	7.2% 23/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	10.1% 33/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Chest pain,not cardio or pleur	5.3% 17/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness (not neuro)	5.6% 18/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Myalgia	7.5% 24/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	6.1% 20/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Dizziness/light headedness	8.1% 26/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	8.9% 29/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Headache	7.8% 25/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	8.6% 28/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Sensory neuropathy	14.0% 45/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	15.9% 52/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Nervous system disorders Taste disturbance	7.2% 23/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	7.6% 25/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Anxiety/agitation	5.3% 17/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Depression	5.3% 17/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	0.00% 0/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Psychiatric disorders Insomnia	8.7% 28/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	8.9% 29/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	15.0% 48/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	13.1% 43/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	33.0% 106/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	30.0% 98/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Skin and subcutaneous tissue disorders Alopecia	41.1% 132/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	62.4% 204/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Skin and subcutaneous tissue disorders Rash/desquamation	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	9.2% 30/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Vascular disorders Hypotension	6.5% 21/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	8.9% 29/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.
Vascular disorders Thrombosis/embolism	0.00% 0/321 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.	5.2% 17/327 • Patients were evaluated for adverse events prior to the beginning of each cycle of treatment, approximately every 4 weeks, for up to a maximum of 4 cycles (16 weeks). Eligible patients who received at least one dose of treatment were included in the analysis of adverse events.

Additional Information

Lung Committee Statistician

SWOG Statistical Center

Phone: 206-667-4623

Results disclosure agreements

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