Pemetrexed Plus Bevacizumab in Non Small Cell Lung Cancer

Inclusion Criteria:

* Histologically or cytologically confirmed,
* Unresectable locally advanced (stage IIIB) or metastatic (stage IV) non-squamous NSCLC
* 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 ≥ 11 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 and give written informed consent

Exclusion Criteria:

* Previous therapy with pemetrexed
* 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