Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer.
• Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens.

• Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1.
• Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43.
• Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43.

At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92.

The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria:

• Medically inoperable stage IIIA
• Unresectable stage IIIA or IIIB
• Measurable disease on three-dimensional planning CT scan
• No post-resection intrathoracic tumor recurrence
• No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure
• No evidence of small cell histology
• No evidence of hematogenous or distant metastases

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Absolute granulocyte count at least 2,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease)

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia

Pulmonary:

• Forced expiratory volume (FEV)_1 greater than 1,000 mL

Other:

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No weight loss of more than 10% in 3 months prior to diagnosis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior thoracic or neck radiotherapy

Surgery:

• See Disease Characteristics
• No prior complete or subtotal tumor resection