Lometrexol Plus Folic Acid in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC)

  • Stage IIIB or IV

    • Squamous cell carcinoma
    • Adenocarcinoma
    • Large cell carcinoma
    • Adenosquamous carcinoma
• Progressive disease after receiving 1 cisplatin- or carboplatin-containing regimen for stage IIIB or IV disease

• Measurable disease

  • At least 1 lesion at least 1 cm x 1 cm by CT scan either not in a previously irradiated field or showing clear evidence of disease progression after radiation
• No symptomatic or rapidly increasing, moderate or large amounts of pleural effusion or ascites
• No prior or concurrent CNS metastases (brain or meningeal)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3*
• Platelet count at least 100,000/mm^3*
• Hemoglobin at least 9.0 g/dL*
• *Without transfusions or growth factors in the previous 7 days

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (regardless of liver involvement secondary to tumor)
• AST and ALT no greater than 2.5 times ULN (5 times ULN if liver has tumor involvement)

Renal:

• Calculated creatinine clearance at least 60 mL/min using Cockroft and Gault formula

Gastrointestinal:

• No inflammatory bowel disease
• No radiation enteritis
• No malabsorption syndrome
• No inability to absorb folic acid

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during study
• No known untreated vitamin B12 deficiency
• HIV negative
• No drug abusers
• No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No severe concurrent disease or major comorbidity that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 3 weeks since prior biologic therapy for NSCLC and recovered from acute side effects
• Prior treatment with an experimental vaccine allowed
• No concurrent routine or prophylactic filgrastim (G-CSF), sargramostim (GM- CSF), or epoetin alfa

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy for NSCLC (6 weeks for mitomycin or nitrosourea) and recovered from acute side effects
• Prior adjuvant or neoadjuvant chemotherapy allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• Recovered from acute side effects of prior radiotherapy
• No prior radiotherapy to 25% or more of bone marrow
• No prior whole pelvic irradiation

Surgery:

• At least 3 weeks since prior major surgery and recovered

Other:

• At least 3 weeks since prior investigational agent
• No concurrent proguanil, trimethoprim, co-trimoxazole, or pyrimethamine