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