Trial Outcomes & Findings for Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Extensive-Stage Small Cell Lung Cancer (NCT NCT00057837)

Last Updated: 2023-07-05

Results Overview

Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

140 participants

Primary outcome timeframe

Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry.

Results posted on

2023-07-05

Participant Flow

The study opened to accrual on March 24, 2004, accrued its first patient on July 14, 2004, and was closed on April 14, 2008 with final accrual of 140 patients.

Participant milestones

Participant milestones
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Overall Study STARTED	70	70
Overall Study Treated	69	68
Overall Study Eligible and Treated	66	66
Overall Study Patients With Response	46	38
Overall Study COMPLETED	39	31
Overall Study NOT COMPLETED	31	39

Reasons for withdrawal

Reasons for withdrawal
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Overall Study Progression/relapse	12	14
Overall Study Adverse Event	2	12
Overall Study Death	5	4
Overall Study Withdrawal by Subject	5	3
Overall Study Alternative therapy	0	1
Overall Study Other complicating disease	2	1
Overall Study Physician Decision	1	0
Overall Study Ineligible	3	3
Overall Study Never started treatment	1	1

Baseline Characteristics

Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=66 Participants Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=66 Participants Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.	Total n=132 Participants Total of all reporting groups
Age, Continuous	60 years n=5 Participants	64 years n=7 Participants	63 years n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	33 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	33 Participants n=7 Participants	74 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry.

Population: Only treated and eligible patients are included in this analysis.

Outcome measures

Outcome measures
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=66 Participants Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=66 Participants Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Proportion of Patients With Objective Response by Solid Tumor Response Criteria (RECIST)	0.697 proportion of participants Interval 0.591 to 0.789	0.576 proportion of participants Interval 0.467 to 0.679

SECONDARY outcome

Timeframe: Assessed every 6 weeks while on treatment, and then every 3 months for patients < 2 years from study entry, every 6 months if patient is 2-3 years from study entry.

Population: Only eligible and treated patients with response are included in this analysis.

Duration of response is defined as the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, taking as reference the smallest measurements recorded since treatment started.

Outcome measures

Outcome measures
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=46 Participants Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=38 Participants Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Duration of Response	6.0 Months Interval 5.0 to 7.0	6.0 Months Interval 5.0 to 8.3

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for 1 years

Population: Only eligible and treated patients are included in this analysis.

Overall survival is defined as the time from randomization to death.

Outcome measures

Outcome measures
Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=66 Participants Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=66 Participants Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Overall Survival	11.9 Months Interval 9.6 to 13.7	11.0 Months Interval 8.6 to 13.1

Adverse Events

PET (Topotecan/Etoposide/Cisplatin/G-CSF)

Serious events: 48 serious events

Other events: 66 other events

Deaths: 0 deaths

PIE (Irinotecan/Cisplatin/Etoposide)

Serious events: 51 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=69 participants at risk Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=68 participants at risk Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Infections and infestations Infection w/ Gr3-4 neutropenia	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Anemia	20.3% 14/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	18.8% 13/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	32.4% 22/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	33.3% 23/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	45.6% 31/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Thrombocytopenia	21.7% 15/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Transfusion: Platelets	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Injury, poisoning and procedural complications Transfusion: PRBCS	26.1% 18/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	16.2% 11/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Cardiac disorders Supraventricular arrhythmias	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypotension	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Thrombosis/Embolism	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Visceral Arterial Ischemia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Cardiac disorders Cardiac-other	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	14.5% 10/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	16.2% 11/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Weight loss	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Constitutional symptoms	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Skin- Other	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations SIADH (The syndrome of inappropriate antidiuretic hormone secretion)	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	11.8% 8/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Dehydration	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	11.8% 8/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dyspepsia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Ileus	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Stomatitis	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o prior colostomy	2.9% 2/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	25.0% 17/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders GI-other	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hemorrhage with Grade 3 or 4 Platelets	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders CNS hemorrhage	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Hemoptysis	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Alkaline phosphatase increased	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin increased	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations AST increased	2.9% 2/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations ALT increased	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Febrile neutropenia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/ unknown ANC	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/o neutropenia	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperkalemia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypermagnesemia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	2.9% 2/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	2.9% 2/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyponatremia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle Weakness	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Confusion	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	2.9% 2/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Depressed level of consciousness	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Depression	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-motor	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Syncope	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdominal Pain	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Ear and labyrinth disorders Earache	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Myalgia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	2.9% 2/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary- Other	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Renal and urinary disorders Renal Failure	0.00% 0/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	1.5% 1/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.

Measure	PET (Topotecan/Etoposide/Cisplatin/G-CSF) n=69 participants at risk Patients receive topotecan intravenously (IV) over 30 minutes on days 1-3; etoposide IV over 60 minutes immediately followed by cisplatin IV over 60 minutes on days 8-10; and filgrastim (G-CSF) subcutaneously daily beginning on day 11 and continuing until blood counts recover.	PIE (Irinotecan/Cisplatin/Etoposide) n=68 participants at risk Patients receive irinotecan IV over 90 minutes and cisplatin IV over 60 minutes on days 1 and 8 and oral etoposide twice daily on days 3 and 10 of each cycle.
Blood and lymphatic system disorders Anemia	94.2% 65/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	94.1% 64/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	76.8% 53/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	86.8% 59/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Lymphopenia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	68.1% 47/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	82.4% 56/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Thrombocytopenia	66.7% 46/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	50.0% 34/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
General disorders Edema	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypotension	8.7% 6/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	8.8% 6/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	72.5% 50/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	77.9% 53/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fever	10.1% 7/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	8.8% 6/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
General disorders Rigors/chills	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Weight gain	7.2% 5/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Weight loss	20.3% 14/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	29.4% 20/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Alopecia	49.3% 34/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	48.5% 33/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Rash/desquamation	8.7% 6/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	31.9% 22/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	47.1% 32/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	26.1% 18/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	22.1% 15/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Dehydration	13.0% 9/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	14.7% 10/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dyspepsia	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dry mouth	8.7% 6/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	2.9% 2/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	60.9% 42/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	72.1% 49/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Stomatitis	20.3% 14/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	14.7% 10/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Taste disturbance	15.9% 11/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	16.2% 11/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	23.2% 16/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	32.4% 22/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o prior colostomy	17.4% 12/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	50.0% 34/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Alkaline phosphatase increased	53.6% 37/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	32.4% 22/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin increased	10.1% 7/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	8.8% 6/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations AST increased	20.3% 14/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	23.5% 16/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations ALT increased	27.5% 19/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	26.5% 18/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/o neutropenia	11.6% 8/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	8.8% 6/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	2.9% 2/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypocalcemia	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	40.6% 28/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	50.0% 34/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyponatremia	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	4.4% 3/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle Weakness	5.8% 4/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Dizziness/Lightheadedness	11.6% 8/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	14.7% 10/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Insomnia	7.2% 5/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Depression	4.3% 3/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	7.4% 5/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-sensory	17.4% 12/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	19.1% 13/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdominal Pain	1.4% 1/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Bone, pain	8.7% 6/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	5.9% 4/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Myalgia	10.1% 7/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Cough	10.1% 7/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	8.8% 6/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.6% 8/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	10.3% 7/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.
Investigations Creatinine increased	21.7% 15/69 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.	19.1% 13/68 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment.