title: A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma.
abstract: OBJECTIVE
  The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ.
  
  
  METHODS
  Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m(2) days 1-7 and 15-21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks.
  
  
  RESULTS
  Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44%) had gross total resection. O(6)-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9% (95% CI 9.3-40.0%). The median PFS and overall survival (OS) were 4.2 months (95% CI 3.6-5.4 months) and 7.3 months (95% CI 5.8-8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19%; 95% CI 7.2-36.4) were long-term survivors, with a median PFS and OS (50% events) of 9.5 months (95% CI 7.9-23.6) and 15.4 (95% CI 8.9-NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed.
  
  
  CONCLUSIONS
  This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.
authors.affiliation: Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Sepúlveda
authors.forename: C
authors.initials: C
authors.lastname: Belda-Iniesta
authors.forename: M
authors.initials: M
authors.lastname: Gil-Gil
authors.forename: P
authors.initials: P
authors.lastname: Pérez-Segura
authors.forename: A
authors.initials: A
authors.lastname: Berrocal
authors.forename: G
authors.initials: G
authors.lastname: Reynés
authors.forename: O
authors.initials: O
authors.lastname: Gallego
authors.forename: J
authors.initials: J
authors.lastname: Capellades
authors.forename: J M
authors.initials: JM
authors.lastname: Ordoñez
authors.forename: B
authors.initials: B
authors.lastname: La Orden
authors.forename: C
authors.initials: C
authors.lastname: Balañá
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006402:Hematologic Diseases; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D000077204:Temozolomide
chemical_list: D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide