Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

OBJECTIVES:

- Determine the tolerability of topotecan and carboplatin with or without filgrastim
(G-CSF) in patients with extensive stage small cell lung cancer.

- Determine response and survival rates in patients treated with these regimens.

OUTLINE: This is a multicenter study. The first 12 patients are assigned to 1 of 2 treatment
regimens (6 per regimen). The next 33 patients receive treatment based on the toxicity
experienced by the first 12.

Regimen A:

- Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes
on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and
continuing for up to 10 days or until blood counts recover.

- Patients are evaluated after the first 3-week course of chemotherapy. If no patient
experiences unacceptable toxicity or febrile neutropenia, or no more than 1 patient
experiences an absolute neutrophil count of less than 500/mm3 for more than 5 days, the
next 6 patients begin treatment on regimen B. Otherwise, all patients receive treatment
as in regimen A.

Regimen B:

- Patients receive topotecan and carboplatin as in regimen A.

- Patients are evaluated after the first 3-week course of chemotherapy. If no patient
experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive
treatment as in regimen B; otherwise, patients receive treatment as in regimen A.

Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of
disease progression or unacceptable toxicity. Patients with disease progression limited to
CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is
complete, chemotherapy resumes.

Quality of life is assessed at baseline and at the beginning of each course of chemotherapy.

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

PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study within 13.5 months.

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed extensive stage small cell lung cancer

- Previously untreated with chemotherapy

- No mixed histology

- Metastatic disease outside the chest

- Contralateral supraclavicular or hilar nodes that cannot be included in a single
radiation port OR

- Cytologically proven malignant pleural effusion

- Measurable disease

- No untreated CNS metastases

- CNS metastases treated with whole-brain radiotherapy (WBRT) allowed after
completion of WBRT

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

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

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

Hepatic:

- AST no greater than 5 times upper limit of normal (ULN)

- Alkaline phosphatase no greater than 5 times ULN

- Bilirubin no greater than 1.5 times ULN OR

- Direct bilirubin no greater than ULN

Renal:

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance at least 50 mL/min

Cardiovascular:

- No uncontrolled angina pectoris

- No congestive heart failure within the past 3 months unless ejection fraction is
greater than 40%

- No uncontrolled cardiac arrhythmias

- No myocardial infarction within the past 3 months

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No clinically significant infection

- No hypersensitivity to E. coli-derived proteins

- No other malignancy within the past 3 years except non-melanoma skin cancer,
carcinoma in situ of the cervix, or localized prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- See Disease Characteristics

- At least 5 years since prior chemotherapy for another malignancy

- No prior nitrosoureas

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- No prior thoracic radiotherapy

- At least 1 day since prior palliative radiotherapy (except to chest)

- No more than 3 fractions to chest for superior vena cava syndrome allowed

- No concurrent radiotherapy (including thoracic radiotherapy)

Surgery:

- More than 3 weeks since prior major surgery