Pemetrexed Disodium Plus Gemcitabine in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

OBJECTIVES:

• Compare the tumor response rates in patients with locally advanced or metastatic non-small cell lung cancer treated with 3 different schedules of pemetrexed disodium and gemcitabine.
• Compare the duration of response, time to progressive disease, time to treatment failure, and survival time in patients treated with these regimens.
• Compare the quantitative and qualitative toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, open-label study. Patients are stratified according to stage of disease (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to one of three treatment arms.

• Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1 followed by gemcitabine IV over 30 minutes on days 1 and 8.
• Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by pemetrexed disodium IV over 10 minutes on day 1.
• Arm III: Patients receive gemcitabine IV over 30 minutes on day 1 and pemetrexed disodium IV over 10 minutes followed by gemcitabine IV over 30 minutes on day 8.

Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive up to 6 additional courses of therapy.

Patients are followed every 2 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 180 patients (60 per treatment arm) will be accrued for this study within 20 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer

• Stage IIIB disease that is ineligible for combined modality therapy OR
• Stage IV disease
• Measurable disease
• No clinically detectable (by physical exam) third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures
• No brain metastases (even if treated)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil 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 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 3 times ULN (5 times ULN if liver metastases present)

Renal:

• Creatinine clearance at least 45 mL/min

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take folic acid or cyanocobalamin (vitamin B12) supplementation
• No uncontrolled infection
• No concurrent chronic debilitating disease
• No weight loss of 10% or more within the past 6 weeks
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic or genetic therapy for lung cancer
• No concurrent immunomodulating agents

Chemotherapy:

• No prior chemotherapy for lung cancer

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy to a different site and recovered
• No prior radiotherapy to 25% or more of bone marrow
• No prior radiotherapy to whole pelvis
• No prior radiotherapy for primary disease
• No concurrent radiotherapy

Surgery:

• More than 4 weeks since prior major surgery

Other:

• No aspirin or nonsteroidal anti-inflammatory agents 2 days before, during, and for 2 days after pemetrexed disodium administration (5 days for long-acting agents such as piroxicam, naproxen, diflunisal, or nabumetone)
• No other concurrent cytostatic or cytotoxic therapy