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

OBJECTIVES:

- Compare the survival of patients with extensive stage small cell lung cancer treated
with cisplatin and irinotecan vs cisplatin and etoposide.

- Compare the objective response rate and progression-free survival of patients treated
with these regimens.

- Compare the toxic effects of these regimens in these patients.

- Determine the association between UGT1A1 polymorphisms and irinotecan-associated toxic
effects in these patients.

- Determine the association between ERCC-1 and XRCC-1 polymorphisms and non-response of
patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number
of metastatic sites (single vs multiple), lactic dehydrogenase (no greater than upper limit
of normal (ULN) vs greater than ULN), and weight loss in the past 6 months (5% or less vs
more than 5%). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 and cisplatin
IV over 30-60 minutes on day 1. Courses repeat every 4 weeks.

- Arm II: Patients receive etoposide IV over 30-60 minutes on days 1-3 and cisplatin IV
over 30-60 minutes on day 1. Courses repeat every 3 weeks.

Treatment in both arms continues for 4 courses in the absence of disease progression or
unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 620 patients (310 per treatment arm) will be accrued for this
study within 4 years.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed extensive stage small cell lung cancer
(SCLC)

- Measurable or evaluable disease by CT scan, MRI, x-ray, physical exam, or nuclear exam

- Brain metastases allowed if previously treated with radiotherapy and/or surgery and
are neurologically stable (i.e., no progressing symptoms and off steroids and
anticonvulsants)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Zubrod 0-1

Life expectancy

- Not specified

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

Hepatic

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST or ALT no greater than 2.5 times ULN

Renal

- Creatinine normal

- Creatinine clearance at least 50 mL/min

Other

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- HIV negative

- No concurrent AIDS-related illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior biologic therapy for SCLC

- No filgrastim (G-CSF) within 24 hours of chemotherapy

Chemotherapy

- No prior systemic chemotherapy for SCLC

Endocrine therapy

- See Disease Characteristics

Radiotherapy

- See Disease Characteristics

- At least 21 days since prior brain radiotherapy and recovered

- No other prior radiotherapy for SCLC

Surgery

- See Disease Characteristics

- At least 21 days since prior thoracic or other major surgery and recovered

Other

- No concurrent enzyme inducing antiepileptic drugs (phenytoin, phenobarbital,
oxcarboxepine, or carbamazepine)