Inclusion Criteria:

- Written informed consent(as approved by the local Ethical Committee)

- Histological type consisting mainly of non-squamous histology defined preferably with
stage IV metastatic disease or stage IIIB in the presence of supraclavicular lymph
nodes according to the parameters of TNM 7th Ed, not amenable to curative therapy

- ECOG PS 0-1

- Adequate bone marrow reserve

- Adequate hepatic, coagulative and renal function

Exclusion Criteria:

- Mixed NSCLC tumors or mixed adenosquamous carcinomas with a predominant squamous
component histotype (NSCLC and SCLC) or adenosquamous forms, with predominant
squamous component

- History of gross hemoptysis <3 months prior to enrollment or history or evidence of
inherited bleeding diathesis or coagulopathy with the risk of bleeding.

- Tumors invading or abutting major blood vessels (based on radiologist assessment)

- Evidence of brain metastases not previously treated with RT (or any loco-regional
treatment)

- Prior neoadjuvant or adjuvant chemotherapy within six months prior to study
enrollment

- Previous radiotherapy in the last month before study entry (except for radiotherapy
to symptomatic bone sites at risk and not covered in the premises of measurable
disease and assessable)

- A major surgery (including open biopsy) in the month preceding study enrollment or
anticipation of a major surgery during the study

- Unable or unwilling to take folic acid or vitamin B12 supplementation

- Unable or unwilling to take corticosteroids

- History of gastrointestinal fistula, perforation, or abscess, inflammatory bowel
disease, or diverticulitis

- Clinically significant third-space fluid collections, for example, ascites or pleural
effusions that cannot be controlled by drainage or other procedures prior to study
entry

- Need for taking or have recently taken (within 10 days of enrollment) aspirin (>325
mg/d), clopidogrel at doses >75 mg/d, dipyramidole, ticlopidine, or cilostazol.
Patients are also excluded if they cannot hold nonsteroidal anti-inflammatory agents,
other than prophylactic therapy with low-dose aspirin, for a 5-day period during each
cycle (8-day period for long-acting agents, such as piroxicam)

- Need for taking or have recently taken (within 10 days of enrollment) fulldose oral
or parenteral anticoagulants or thrombolytic agents for therapeutic purposes.
Prophylactic use of anticoagulants is allowed; international normalized ratio (INR)
should be <1.5 at study enrollment

- History of thrombotic disorders within the last 6 months prior to entry History of
hypertension, unless hypertension is well controlled study entry (≤150/90 mm Hg) and
the patient is on a stable regimen of antihypertensive therapy. Patients should not
have any prior history of hypertensive crisis or hypertensive encephalopathy

- Serious cardiac condition, such as myocardial infarction within 6 months, angina, or
heart disease, as defined by the New York Heart Association Class III or IV

- Serious concomitant systemic disorder (for example, active infection including human
immunodeficiency virus) that, in the opinion of the investigator, would compromise
the patient's ability to adhere to the protocol

- Receiving concurrent administration of any other antitumor therapy

- Have a second primary malignancy that is clinically detectable at the time of
consideration for study enrollment

- Have had a prior malignancy other than NSCLC, carcinoma in situ of the cervix, or
nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively
treated at least 5 years previously with no subsequent evidence of recurrence.
Patients with a history of low grade (Gleason score ≤6) localized prostate cancer
will be eligible even if diagnosed less than 5 years previously

- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies