Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence

Neurology. 2008 Mar 4;70(10):779-87. doi: 10.1212/01.wnl.0000304121.57857.38.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / toxicity
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / toxicity
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Bevacizumab
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / physiopathology
  • Clinical Trials as Topic / statistics & numerical data
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / physiology
  • Drug Synergism
  • Female
  • Glioma / drug therapy*
  • Glioma / pathology
  • Glioma / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / physiopathology
  • Neoplasm Recurrence, Local / prevention & control
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab