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