Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed primary lung carcinoma

- Non-squamous histology

- Advanced disease defined as stage IIIB disease with cytologically documented
malignant pleural or pericardial effusion or stage IV disease

- Available pathology block or unstained slides from initial or subsequent diagnosis

- Must have undergone ≥ 1 core biopsy

- No patients whose diagnosis was made through a fine-needle aspirate

- No uncontrolled pleural effusions, ascites, or third-space fluid collections

- Meets 1 of the following criteria:

- Non-smoker, defined as patients who smoked ≤ 100 cigarettes in their lifetime

- Former light smoker, defined as patients who smoked between > 100 cigarettes AND
≤ 10 pack-years AND quit ≥ 1 year ago

- No known CNS disease, except for treated brain metastases meeting the following
criteria:

- No evidence of progression or hemorrhage after treatment

- No ongoing requirement for dexamethasone as ascertained by clinical examination
and brain imaging (MRI or CT scan) during the screening period

- Stable doses of anticonvulsants are allowed

- Treatment for brain metastases may include whole-brain radiotherapy,
radiosurgery (gamma knife, LINAC, or equivalent), or a combination as deemed
appropriate by the treating physician

- No patients with CNS metastases treated by neurosurgical resection

- No brain biopsy within the past 3 months

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 2.5 times ULN

- Calculated creatinine clearance > 45 mL/min OR creatinine ≤ 1.5 times ULN

- PT/INR ≤ 1.5 times ULN

- PTT ≤ ULN

- Urine protein:creatinine ratio ≤ 1.0

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Patients with a history of hypertension are eligible provided it is well controlled
(BP < 150/100 mm Hg) on a stable regimen of antihypertensive therapy

- No history of hypertensive crisis or hypertensive encephalopathy

- Able and compliant with folic acid and B12 supplementation

- Able to swallow tablets intact or dissolved in water

- No dysphagia or active gastrointestinal (GI) disease or disorder that alters GI
motility or absorption

- No lack of integrity of the GI tract (e.g., a significant surgical resection of the
stomach or small bowel)

- No abdominal fistula, GI perforation, or intraabdominal abscess within the past 6
months

- None of the following:

- Ongoing or active infection

- Symptomatic congestive heart failure (NYHA class II-IV)

- Cardiac arrhythmia

- Psychiatric illness, social situations, or any other medical condition that
would limit compliance with study requirements

- No myocardial infarction or other evidence of arterial thrombotic disease (angina)
within the past 6 months

- No history of cerebral vascular accident or transient ischemic attack within the past
6 months

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

- No history of bleeding diathesis or coagulopathy

- No ongoing hemoptysis, defined as ≥ ½ teaspoon of bright red blood

- Patients with procedure-related hemoptysis that has resolved post-procedure are
eligible

- No serious nonhealing wound, ulcer, bone fracture, or significant traumatic injury
within the past 28 days

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy

- Patient must be chemotherapy naive

- Prior neoadjuvant or adjuvant chemotherapy allowed provided it was completed ≥ 6
months ago

- No prior anti-VEGF therapy

- At least 3 weeks since prior major surgery

- At least 1 week since prior radiotherapy

- More than 28 days since prior and no concurrent treatment with an investigational
agent

- More than 7 days since prior core biopsy

- Concurrent daily treatment with aspirin or NSAIDs are eligible provided patients are
able to interrupt NSAIDs 2 days before (5 days for long-acting NSAIDs), the day of,
and for 2 days following the administration of pemetrexed disodium

- No concurrent treatment with dipyridamole (Persantine), ticlopidine (Ticlid),
clopidogrel (Plavix), and/or cilostazol (Pletal)