Therapeutic Strategies in Patients With Non-squamous Non-small Cell Lung Cancer With Brain Metastases

Inclusion Criteria:

1. Patients with histologically or cytologically proven non-epidermoid, non-small celllung cancer, non-EGFR (Epidermal Growth Factor Receptor)-mutated (or mutation testimpracticable).

2. Patients with brain metastasis/metastases without neurosurgical indication.

3. Asymptomatic patients (without treatment or with stable steroids or antiepileptictreatments for ≥ 5 days prior to obtaining the baseline MRI of the brain, and ≥ 5 daysprior to first dose of study treatment (Cycle 1, Day 1).

4. At least one lesion measurable according to the RECIST (Response Evaluation Criteriain Solid Tumors) criteria.

5. ECOG (Eastern Cooperative Oncology Group) Performance Status 0 - 1

6. No previous chemotherapy for this cancer, apart from adjunctive chemotherapy more than 18 months ago.

7. Prior surgery is authorized in case of documented recurrence or progression.

8. Adequate biological functions (hematologic, platelets, hemoglobin, hepatic function,alkaline phosphatases, ASAT (Aspartate transaminase) and ALAT (AlanineAminotransferase); creatinine clearance).

9. For women: Effective contraception for women of childbearing age during treatment andfor 6 months following treatment. For men: They must be surgically sterile or accept the use of effective contraceptionuntil 6 months after the treatment period.

10. Patients of more than 18 years of age.

11. Estimated survival of at least 12 weeks.

12. Consent signed by the patient

Exclusion Criteria:

1. Patients presenting with a brain lesion eligible for curative treatment (neurosurgical).

2. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.

3. Epidermoid carcinoma.

4. Con indication of Bevacizumab is furthermore

5. Patients presenting with a brain lesion eligible for curative treatment (neurosurgeryor radiosurgery).

6. Symptomatic brain metastasis/metastases in spite of symptomatic treatment.

7. Epidermoid carcinoma.

8. Cons indication of Bevacizumab

9. Inability to take the folic acid or vitamin B12 vitamin supplementation or thedexamethasone premedication (or any equivalent corticosteroid), or any inability tocomply with the study procedures.

10. History of cancer, with the exception of cervical cancer in situ, skin cancer otherthan melanoma, adequately treated low-grade prostatic cancer (Gleason score <6),unless this cancer was diagnosed and treated more than 5 years ago without any signsof recurrence.

11. Patients presenting with a systemic disorder which, in the investigator's opinion,compromises their participation in the study for reasons related to treatment safetyor compliance.

12. Patients incapable of discontinuing their aspirin treatment when the dose is > 1300mg/day or their non-steroidal anti-inflammatory treatment two days before the day, onthe day and two days the day of administration of pemetrexed (Alimta).

13. Patients presenting with a 3rd sector (pleural effusion, ascites) which is clinicallydetectable and uncontrollable by simple measures of the evacuatory puncture type orother treatment before inclusion in the study.

14. Patients presenting with neuropathy of grade > 2 according to the criteria of CTC (Common toxicity Criteria) v3.0.

15. Patients whose foreseeable compliance or geographical distance renders monitoringdifficult.

16. Pregnant or breast-feeding women.

17. Significant weight loss (≥ 10%) during the 6 weeks preceding inclusion in the study.

18. Vaccination against yellow fever within 30 days preceding inclusion in the study.

19. Cons-indication to taking steroids

20. Persons deprived of their liberty as a result of a judicial or administrative decision

21. Concomitant participation in another trial