Pemetrexed Plus Cisplatin for Brain Metastasis of Advanced Non - Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

• Patients with cytologically or histologically confirmed NSCLC.

• Patient with brain metastasis not amenable to surgery or radiosurgery with curativeintent

• At least one brain measurable lesion using RECIST criteria

• ECOG Performance Status ≤2

• No prior chemotherapy for this cancer

• Prior surgery is allowed provided there is a relapse or progression after theprocedure.

• Adequate organ function including the following: Adequate bone marrow reserve:absolute neutrophil count (ANC) superior or equal to 1.5 X109/L, platelets superior orequal to 100 X 109/L, and hemoglobin superior or equal to 9 g/dL; Hepatic: bilirubin <1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartatetransaminase (AST) and alanine transaminase (ALT) <3xULN (or <5xULN with livermetastases); Renal: Calculated creatinine clearance (CrCl) superior or equal to 45mL/min based on the standard Cockroft and Gault formula

• Signed informed consent document from the patient

• Patient must be at least 18 years of age.

• Estimated life expectancy of at least 12 weeks.

• Effective contraception (men and women) for and during the 6 months following the endof treatment

Exclusion Criteria:

• Symptomatic brain metastasis

• Have received prior radiotherapy for brain metastasis

• Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol orstudy related procedures.

• A prior malignancy other than NSCLC, except carcinoma in situ of the cervix ornon-melanoma skin cancer, adequately treated low grade [Gleason score <6] localizedprostate cancer, unless that prior malignancy was diagnosed and definitively treatedat least 5 years previously with no subsequent evidence of recurrence

• Serious concomitant systemic disorders (for example, active infection or abnormalelectrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of theinvestigator, would compromise the safety of the patient and his/her ability tocomplete study.

• Inability to discontinue administration of aspirin at a dose >1.3g/day or othernon-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days afterthe dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).

• Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion,which can be detected clinically (during physical examination), and which cannot beadequately controlled by drainage or other procedures prior to inclusion in the study.

• Peripheral neuropathy > CTC Grade 2

• Patient compliance or geographic distance precluding adequate follow up.