Paclitaxel, Carboplatin Plus Bevacizumab in Pretreated, Advanced or Metastatic Non Small Cell Lung Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB) or metastatic (stage IV) non-squamous NSCLC
• Non-squamous histologic type
• At least one and no more than two previous chemotherapy regimens for advanced or metastatic NSCLC
• Measurable disease, defined as at least 1 bidimensionally measurable lesion ≥ 20 X 10 mm.
• Age ≥ 18 years
• Performance status (WHO) 0-2
• Life expectancy of at least 12 weeks
• Adequate bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3, Hgb ≥ 9 g/dL), liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 2.5 upper normal limit in the absence of liver metastases or ≤ 5 upper normal limit in the presence of liver metastases), and renal function (Creatinine ≤ 1,5 upper normal limit)
• Patients must be able to understand the nature of this study
• Written informed consent

Exclusion Criteria:

• Previous therapy with paclitaxel in combination with carboplatin
• Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
• Pregnant or lactating women
• Any serious, uncontrolled comorbidity on the investigator's judgment
• Uncontrolled infection
• Any sustained chronic toxicity > grade 2 according to the NCI CTCAE (version 3.0)
• Symptomatic neuropathy > grade 2 according to the NCI CTCAE (version 3.0)
• Brain metastases, except if radiated and asymptomatic
• Radiotherapy within the previous 4 weeks
• Previous radiotherapy to the only measurable lesion
• Proteinuria ≥ 500 mgr of protein daily
• Hemoptysis > 10 cc per event
• Clinically significant hematemesis
• Centrally located lesion or in contact with major vessels
• Pulmonary lesion with cavitation
• Documented hemorrhagic diathesis or coagulation disorder
• Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF < normal, ventricular arrhythmia, uncontrolled hypertension)
• Thrombotic event within the previous 6 months
• Concurrent use of aspirin > 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents
• Concurrent treatment with other anti-cancer drug
• Major surgical procedure within the previous 4 weeks