Vanderbilt-Ingram Cancer Center

The purpose of this study is to find out the best maintenance therapy for patients with advanced stage non-small cell lung cancer. Maintenance therapy is usually given after 4 cycles of standard chemotherapy (1 cycle = 21 days) to keep the disease under control for a longer duration. This study will compare the effects, good and/or bad, of bevacizumab, pemetrexed or the combination of the two agents when given as maintenance therapy.

Criteria
 DISEASE CHARACTERISTICS:

 • Cytologically or histologically confirmed non-small cell lung cancer (NSCLC)

 • Predominant non-squamous histology

 • NSCLC not otherwise specified allowed

 • Mixed tumors are categorized by the predominant cell type

 • Must meet 1 of the following criteria:

 • Stage IV disease including M1a or M1b stages or recurrent disease

 • Stage IIIB (T4NX) disease with ipsilateral lung lobe allowed provided patients are not candidates for combined chemotherapy or radiotherapy

 • Measurable or non-measurable disease as defined by RECIST criteria

 • Patient must have an overall stable or better response after 4 courses of induction therapy

 • No cavitary lesions in the lungs

 • Patients with brain metastasis must have received local therapy to the brain and have no evidence of progression in the brain for at least 2 weeks from the time of completion of local therapy, prior to registration

 PATIENT CHARACTERISTICS:

 • ECOG performance status 0-1

 • Leukocytes ≥ 3,000/mm^3

 • ANC ≥ 1,500/mm^3

 • Platelet count ≥ 100,000/mm^3

 • Total bilirubin ≤ institutional upper limit of normal (ULN)

 • AST and ALT ≤ 3 times ULN

 • Creatinine ≤ institutional ULN OR creatinine clearance ≥ 60 mL/min

 • Urine protein:urine dipstick ≤ 0-1+ (if > 1+, urine protein creatinine ratio must be < 1)

 • Not pregnant or nursing

 • Negative pregnancy test

 • Fertile patients must agree to abstain from sexual intercourse or to use adequate contraceptive methods during and for at least 6 months after completion of study therapy

 • No prior malignancy within the past 3 years except superficial melanoma, basal cell carcinoma, or carcinoma in situ

 • No major hemoptysis within the past 4 weeks

 • No uncontrolled intercurrent illness including, but not limited to, any of the following:

 • Ongoing or active infection

 • Symptomatic congestive heart failure

 • Unstable angina pectoris

 • Serious cardiac arrhythmia

 • Psychiatric illness and/or social situations that would limit compliance with study requirements

 • Patients with hypertension must be adequately controlled (BP < 150/100 mm Hg) with appropriate anti-hypertensive therapy or diet

 • No history of arterial thrombotic events or major bleeding within the past 12 months

 • No significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within the past 6 months

 • No significant traumatic injury in the past 3 months

 • No clinically significant cardiovascular disease

 • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

 • No history of serious non-healing wounds, ulcers, or bone fractures

 PRIOR CONCURRENT THERAPY:

 • See Disease Characteristics

 • At least 12 months since prior adjuvant chemotherapy

 • At least 2 weeks since prior radiotherapy

 • Patients must not have had any major surgery such as thoracotomy, laparotomy, craniotomy, or significant traumatic injury within 6 weeks prior to registration

 • Biopsy procedures and chest tube insertion are not considered major surgery for the purpose of this protocol

 • More than 7 days since a core biopsy

 • Concurrent therapeutic anti-coagulation allowed

 • No prior systemic chemotherapy for advanced stage lung cancer

 • No prior paclitaxel, pemetrexed disodium, or bevacizumab

 • Prior carboplatin allowed provided it was given as part of adjuvant chemotherapy

 • No concurrent anti-retroviral therapy in patients with HIV infection