Pemetrexed Disodium and Bevacizumab in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

DISEASE CHARACTERISTICS:

• Histologically or cytologically diagnosed stage IIIB or IV non-small cell lung cancer

  • Stage IIIB patients must have pleural effusion

    • No symptomatic serosal effusion (grade 2 dyspnea) that is not amenable to drainage
  • Mixed histology allowed if all components consistent with non-small cell lung cancer
  • Tumors with squamous cell histology feature are allowed

• Must have measurable disease with at least one lesion with a longest diameter accurately measured as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT

  • Large ( > 4 cm) centrally located lesions or large lesions in close proximity to major blood vessels should receive palliative radiation

    • The irradiated lesion should not be a target lesion
• Previously treated with one chemotherapy regimen in the neoadjuvant, adjuvant, or advanced disease setting

• No symptomatic, untreated, or uncontrolled CNS metastases

  • CNS metastases treated with prior whole brain radiotherapy allowed

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/ mm^3
• Hemoglobin ≥ 9 g/dL
• 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
• Urine protein:creatinine ratio < 1.0
• Pregnant or nursing women are ineligible
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation
• No seizure disorder
• No clinically significant infection
• No other second primary malignancy within the past 5 years except carcinoma in situ of the cervix, non-melanomatous skin cancer, or low-grade (Gleason score ≤ 6) localized prostate cancer
• No hypertension or labile hypertension
• No history of poor compliance with antihypertensive medications
• No angina pectoris
• No congestive heart failure within the past 3 months unless ejection fraction > 40%
• No myocardial infarction within the past 6 months
• No cardiac arrhythmia
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung

• No active or recent history of hemoptysis

  • Hemoptysis resolved > 2 weeks ago with measures such as palliative radiation therapy (i.e., 3,000 cGy over 10 fractions), arteriographic embolization, or endobronchial interventions (e.g., photodynamic therapy or brachytherapy) is acceptable
• No diabetes
• No prior serious, non-healing wounds, ulcers, or bone fractures
• No history of stroke within the past 6 months
• No history of abdominal fistula or gastrointestinal perforation
• No intra-abdominal abscess within the past 6 months
• Not at greater than average risk of bleeding
• No significant traumatic injury within the past 4 weeks

PRIOR CONCURRENT THERAPY:

• No aspirin at doses ≥ 1.3 grams per day within 10 days prior to or 10 days after pemetrexed disodium treatment
• No chemotherapy within the past 3 weeks (6 weeks for mitomycin C or nitrosoureas)
• No immunotherapy or biologic therapy within the past 2 weeks

• No full field radiation therapy within the past 4 weeks or limited field radiation therapy within the past 2 weeks

  • The site of previous radiotherapy should have evidence of progressive disease if it is the only site of disease
• No prior post pelvic radiation
• No prior use of pemetrexed disodium
• No prior radiation to > 25% of the marrow cavity
• No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks
• No minor surgery within the past 2 weeks except insertion of a vascular access device
• No concurrent major surgery
• No other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational within the past 4 weeks
• No concurrent use of Hypericum perforatum (St. John's wort)

• No concurrent anticoagulant use

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