A Phase II Multicenter Study Of Lometrexol Sodium And Folic Acid In Subjects With Previously Treated Stage IIIB or IV Non-Small Cell Lung Cancer

Inclusion Criteria

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