DISEASE CHARACTERISTICS:

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

  • Stage IIIB or IV disease
• Must have evidence of disease progression after first-line therapy

• Measurable or non-measurable disease

  • Measurable disease is defined as lesions that can be accurately measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan

  • Non-measurable disease is defined as all other lesions, including small lesions (i.e., longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan) and truly non-measurable lesions, including any of the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural or pericardial effusion
    • Lymphangitis cutis or pulmonis
    • Abdominal mass that are not confirmed and followed by imaging techniques
    • Cystic lesions
• No cavitary lesions
• No pleural effusions or ascites detectable on physical exam

• No symptomatic or untreated CNS metastases

  • Patients with CNS metastases are eligible provided the metastases were definitively treated with surgery or radiotherapy AND patient is asymptomatic and off steroids or on a stable dose of steroids for 2 weeks prior to study entry
• Concurrent enrollment on CALGB-580702 (imaging study) required

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Magnesium ≥ lower limit of normal
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• PTT ≤ 1.5 times ULN
• INR ≤ 1.5
• Creatinine clearance ≥ 45 mL/min
• Quantitative urine protein < 30 mg/dL OR ≤ 1+ on dipstick
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study therapy
• QTc interval ≤ 500 msec
• No ongoing cardiac dysrhythmias
• No atrial fibrillation

• No symptomatic congestive heart failure within the past 12 months

  • NYHA class I heart failure allowed

  • Patients with a history of NYHA class II heart failure are eligible provided at least 1 of the following criteria is met:

    • Asymptomatic on treatment
    • Previously treated with anthracycline
    • Previously treated with central thoracic radiotherapy that included the heart in the radiotherapy port
• No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft or stenting, cerebrovascular accident, or transient ischemic attack within the past year
• No hypertension that cannot be controlled by medications (i.e., blood pressure > 150/100 mm Hg despite optimal medical therapy)
• No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome

• No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis

  • Patients with blood-tinged or blood-streaked sputum are eligible provided the hemoptysis is < 5 mL of blood per episode and < 10 mL of blood per 24-hour period, in the best estimate of the investigator
• No interstitial pneumonitis or pulmonary fibrosis on baseline CT scan
• No abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, or serious or non-healing wound, ulcer, or bone fracture within the past 28 days
• History of hypothyroidism allowed provided patient is currently euthyroid

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 28 days since prior first-line therapy

  • No more than one prior chemotherapy regimen (platinum or non-platinum based) in the first-line setting for NSCLC
• Prior adjuvant therapy allowed provided the patient received one regimen in the advanced setting
• At least 4 weeks since prior EGFR inhibitors or bevacizumab
• At least 28 days since prior major surgery (6 weeks since resection of brain metastases)
• At least 14 days since prior radiotherapy

• More than 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:

  • Azole antifungals (e.g., ketoconazole or itraconazole)
  • Diltiazem
  • Clarithromycin
  • Erythromycin
  • Verapamil
  • Delavirdine
  • HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir, or nelfinavir)

• More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:

  • Rifampin
  • Rifabutin
  • Carbamazepine
  • Phenobarbital
  • Phenytoin
  • St. John's wort
  • Efavirenz
  • Tipranavir
• No prior pemetrexed disodium
• No prior VEGFR inhibitors (e.g., semaxanib, SU6668, AZ6474, sunitinib malate, vatalanib, cediranib, AEE-788, or sorafenib)
• No concurrent chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function
• No concurrent dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), and/or cilostazol (Pletal)

• No concurrent therapeutic anticoagulation for thromboembolic disease

  • Concurrent low-dose warfarin (≤ 2 mg/day) allowed for prophylaxis of thrombosis
• No concurrent agents with proarrhymthic potential (e.g., quinidine, procainamide, disopyramide, sotalol, probucol, bepridel, haloperidol, risperidone, indapamide, or flecainide)
• No concurrent hormonal therapy, except steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or dexamethasone used intermittently as an antiemetic or as premedication for pemetrexed disodium
• No other concurrent chemotherapy
• No concurrent palliative radiotherapy
• No concurrent G-CSF (filgrastim), GM-CSF (sargramostim), and/or pegfilgrastim