Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed nonsquamous cell non-small cell lung cancer
(NSCLC)

- Stage IIIB (with pleural effusion) or IV disease

- Squamous cell carcinomas not allowed

- Adenosquamous histology allowed

- Clinically significant effusion (e.g., symptomatic pleural effusion or ascites)
allowed provided it is drained before study treatment

- No symptomatic pleural and/or peritoneal effusion (≥ grade 2 dyspnea, as defined
by NCI CTCAE v3.0 criteria) that is not amenable to drainage

- If effusion produces clinically significant measurable objective changes, such
as hypoxia or estimated volume > 500 mL, effusion should be drained even if
asymptomatic

- Measurable disease, defined as ≥ 1 lesion with longest diameter ≥ 2.0 cm by
conventional techniques or ≥ 1.0 cm by spiral CT scan

- If the sole site of disease is in a previously irradiated field, must have
evidence of disease progression/recurrence within the irradiated field OR
presence of a new lesion outside the irradiated field

- No symptomatic, untreated, or uncontrolled CNS metastases

- CNS metastases that were previously treated with whole brain radiotherapy (WBRT)
allowed

- Willing to enroll in NCCTG-N0392

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Life expectancy ≥ 12 weeks

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

- AST and ALT ≤ 3 times ULN (≤ 5 times ULN if liver has tumor involvement)

- Creatinine clearance ≥ 45 mL/min

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Able to take folic acid, vitamin B_12 supplementation, or dexamethasone

- Able to complete questionnaire(s) alone or with assistance

- Willing to provide biologic specimens as required by the study

- Willing to return to NCCTG participating center for follow-up

- No clinically significant infection

- No serious, nonhealing wounds, ulcers, or bone fractures

- No seizure disorder

- No second primary malignancy within the past 5 years, except for any of the
following:

- Carcinoma in situ of the cervix

- Nonmelanomatous skin cancer

- History of melanoma allowed only if diagnosed and definitively treated ≥ 5
years ago with no subsequent evidence of recurrence

- Low-grade (Gleason score ≤ 6) localized prostate cancer (no nodal involvement)

- Previously treated stage I breast cancer

- No concurrent severe and/or uncontrolled medical condition, including any of the
following:

- Hypertension, labile hypertension, or history of poor compliance with
antihypertensive medication

- Angina pectoris

- Congestive heart failure within the past 3 months, unless ejection fraction >
40%

- Myocardial infarction within the past 6 months

- Cardiac arrhythmia

- Diabetes mellitus

- Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the
lung

- Active or recent history of hemoptysis > ½ teaspoon per event

- Ongoing or active infection

- Psychiatric illness/social situation that would limit compliance with study
requirements

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 12 months

- No diverticulitis within the past 12 months

- No stroke within the past 6 months

- No significant traumatic injury within the past 8 weeks

- Not at greater than normal risk of bleeding

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy to > 25% of bone marrow

- More than 2 weeks since prior radiotherapy and recovered (alopecia allowed)

- At least 2 weeks since prior WBRT

- At least 3 days since prior gamma knife radiosurgery (without WBRT) for brain
metastases

- More than 4 weeks since prior administration of live or attenuated viral vaccine

- More than 8 weeks since prior major surgery (e.g., laparotomy) or open biopsy (> 4
weeks since minor surgery)

- Insertion of a vascular access device allowed

- No prior chemotherapy or systemic therapy for advanced lung cancer, except
neoadjuvant or adjuvant chemotherapy

- No NSAID's 2 days prior to (5 days for long-acting NSAID's), the day of, and 2 days
following protocol treatment

- More than 12 months since prior neoadjuvant therapy, adjuvant therapy, systemic
chemotherapy, chemoradiotherapy, immunotherapy, or biologic therapy

- No concurrent anticoagulants

- Low-dose warfarin or heparin for deep venous thrombosis prophylaxis allowed