Combination Chemotherapy With or Without Tirapazamine in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

OBJECTIVES:

• Compare the effects of paclitaxel and carboplatin with or without tirapazamine on progression-free survival and overall survival in patients with stage IV and selected stage IIIB non-small cell lung cancer.
• Compare response rates in patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to weight loss (less than 5% vs 5% or more), stage of disease (IIIB vs IV), and lactate dehydrogenase level (normal vs abnormal). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive tirapazamine IV over 2 hours followed by paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1.
• Arm II: Patients receive paclitaxel and carboplatin as in arm I. Treatment continues every 21 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for one year, and then every 6 months for 2 years, or until death.

PROJECTED ACCRUAL: Approximately 500 patients (250 per arm) will be accrued for this study within 20 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven newly diagnosed advanced primary non-small cell lung cancer (NSCLC), including the following cellular types:

• Adenocarcinoma
• Large cell carcinoma
• Squamous cell carcinoma
• Unspecified carcinoma OR
• Recurrent disease after prior surgery and/or radiotherapy
• Stage IIIB disease

• T4 lesion due to malignant pleural effusion OR
• Stage IV disease

• Any T, any N, M1 (distant metastasis, including lesions in multiple lobes of the ipsilateral lung)
• Measurable or evaluable disease

• Pleural effusions, ascites, and laboratory parameters not considered as only evidence of disease
• Must be outside prior radiated field or area of prior surgical resection or new lesion must be present
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN

Renal:

• Creatinine no greater than ULN
• Creatinine clearance at least 50 mL/min

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No peripheral neuropathy (motor or sensory) of grade 2 or greater
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I/II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy for NSCLC

Chemotherapy:

• No prior systemic chemotherapy for NSCLC

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 2 weeks since prior thoracic or other major surgery and recovered