Cisplatin/Vinorelbine/Bevacizumab Followed by Docetaxel/Gemcitabine/Bevacizumab Versus the Cisplatin/Docetaxel/Bevacizumab Combination in Locally Advanced or Metastatic NSCLC

Inclusion Criteria:

* Histologically confirmed, unresectable locally advanced (stage IIIB with pleural effusion) or metastatic (stage IV) non-squamous NSCLC
* Performance status (WHO) 0-1
* Adequate bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 11 g/dL), liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 2.5 UNL, ALP ≤ 5 UNL), and renal function (Creatinine ≤ UNL - if borderline, creatinine clearance should be ≥ 60 mL/min)
* No previous chemotherapy or immunotherapy for advanced/metastatic NSCLC is allowed

  --Previous radiotherapy is allowed provided that the measurable lesions are outside the radiation fields
* Measurable disease, defined as at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm
* Patient able to take oral medication
* Absence of active CNS disease
* Paraffin embedded sample of primary or metastatic tumor diagnostic specimen must be available
* Patients must be able to understand the nature of this study and give written informed consent

Exclusion Criteria:

* Pregnant or lactating women
* Women of child-bearing age unable or unwilling to take effective contraceptive measures
* Active CNS disease, brain metastases, or leptomeningeal involvement
* Symptomatic neuropathy \> grade1 according to the NCI CTCAE (version 3.0)
* Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, LVEF \< normal, uncontrolled hypertension, ventricular arrhythmia), anticoagulation treatment or thrombotic event within the previous 6 months
* Active infection, requiring IV antibiotic treatment, within the previous 2 weeks
* Long-term oxygen therapy
* Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
* Radiotherapy within the previous 4 weeks
* Previous radiotherapy to the only measurable lesion
* Concurrent treatment with other anti-cancer drug
* Uncontrolled hypercalcemia
* Known allergy to drugs with similar chemical structure to study drugs. Concurrent corticosteroids, except for chronic therapy with methylprednisolone ≤ 20 mgr daily (or equivalent) for more than one month