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