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