title: Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence.
abstract: BACKGROUND
  Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor.
  
  
  METHODS
  We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone.
  
  
  RESULTS
  A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders.
  
  
  CONCLUSIONS
  Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.
authors.affiliation: Department of Neurology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, SW430B, 44 Binney St., Boston, MA 02115, USA. anorden@partners.org
authors.forename: A D
authors.initials: AD
authors.lastname: Norden
authors.forename: G S
authors.initials: GS
authors.lastname: Young
authors.forename: K
authors.initials: K
authors.lastname: Setayesh
authors.forename: A
authors.initials: A
authors.lastname: Muzikansky
authors.forename: R
authors.initials: R
authors.lastname: Klufas
authors.forename: G L
authors.initials: GL
authors.lastname: Ross
authors.forename: A S
authors.initials: AS
authors.lastname: Ciampa
authors.forename: L G
authors.initials: LG
authors.lastname: Ebbeling
authors.forename: B
authors.initials: B
authors.lastname: Levy
authors.forename: J
authors.initials: J
authors.lastname: Drappatz
authors.forename: S
authors.initials: S
authors.lastname: Kesari
authors.forename: P Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab