Neo-adjuvant Treatment With Temozolomide and Bevacizumab Previous to Temozolomide Plus Radiation Plus Bevacizumab Therapy in Unresectable Glioblastoma

Inclusion criteria

• Patients with glioblastoma, non-resectable, biopsy only. Accepting a craniotomy with resection attempted if an RMN within a period of about 72 hours to confirm that the resection was less than 25% of the tumor and fulfill criterion
• Measurable disease and contrast uptake ≥ 3 cm in one of its diameters.
• Stable doses of dexamethasone during the week prior to inclusion.
• Performance Status ≤ 2.
• Age ≤ 75 years.
• MiniMental Status> 25/30.
• Bartel index > 50%.
• The surgical incision should be healed prior to randomization. The treatment can be started at 3 weeks of a simple stereotactic biopsy or 4 weeks in case of open biopsy (craniotomy).
• Maximum baseline MRI performed 4 weeks before starting treatment (acceptance of the MRI done for neuronavegation biopsy as baseline).
• Adequate bone marrow reserve: neutrophils>2000x109/L, platelets>100x109/L, hemoglobin≥106g/dl.
• Not received prior treatment with chemotherapy or radiation.
• Adequate renal function: Creatinine <1.5 ULN of the laboratory performing the analysis.
• Adequate liver function: Serum bilirubin <1.5/ULN SGOT, SGPT<2.5ULN. Serum alkaline phosphatase<3/ULN.
• Absence of proteinuria.
• Effective method of contraception for patients and their partners.
• Written informed consent
• Collecting material for a double histological confirmation of diagnosis.

Exclusion criteria

• Prior radiotherapy or chemotherapy for the treatment of glioma.
• Less than 5 years prior to any invasive neoplasia. Accepted carcinoma in situ of cervix carcinoma or cutaneous vasocelular.
• Cerebral hemorrhage after biopsy.
• Pregnancy or lactation.
• Clinically significant cardiovascular disease: - Myocardial infarction or unstable angina (≤ 6 months before randomization) - Congestive heart failure (CHF) class ≥ II NYHA, New York Heart Association. - Cardiac Arrhythmia uncontrolled despite medication (may include patients with atrial fibrillation often controlled). - Peripheral vascular disease ≥ grade 3 (ie, symptomatic and interfering with everyday activities or specifying repairs or review).
• Continued use of aspirin> 325 mg / day, currently or recently (within the 10 days prior to randomization).
• Currently established treatment with therapeutic doses of anticoagulants Coumarin derivatives (courmarina, warfarin) or a week before starting treatment. It allows the administration of heparin for control of Deep Vein Thrombosis (DVT)
• Patients with PTSD and patients with inflammatory bowel disease, with risk of perforation.
• HT with values above 150 mmHg systolic pressure of 100 mmHg and diastolic tension is not controllable with standard antihypertensive drugs.
• Not healed scars, ulcers or recent bone fracture.
• Bleeding diathesis or coagulopathy.