Bevacizumab and central nervous system (CNS) hemorrhage

Cancer Chemother Pharmacol. 2013 Jun;71(6):1561-5. doi: 10.1007/s00280-013-2155-4. Epub 2013 Apr 6.

Abstract

Background: Bevacizumab is widely used and may cause life-threatening bleeding. We attempted to identify clinical characteristics associated with central nervous system (CNS) hemorrhage in a broad population.

Methods: We performed a retrospective review of the FDA MedWatch database of adverse events reported with bevacizumab from 11/1997 to 5/2009. Our search used keywords: bleeding, hemorrhage, cerebral, intracranial, subarachnoid, cerebellar, hemorrhagic stroke and brain.

Results: A total of 17,466 reports were included in the database: 154 described CNS hemorrhage in 99 patients, and 1,041 reports described non-CNS bleeds. Median age was 62 years, and the primary cancers were consistent with indications for bevacizumab. Patients received a median of three (1-36) doses of bevacizumab prior to the bleed. Thirty percent had documented history of hypertension. Sixteen patients with CNS hemorrhage were reported to have CNS metastases. Death was reported as a complication of hemorrhage in 48 %. The most common predisposing factor for CNS bleeds was use of medications associated with bleeding, followed by thrombocytopenia.

Conclusion: In this database, 154 of 1,195 reports of bleeding associated with bevacizumab described a CNS bleed. Although CNS bleeds were not common, they were the reported cause of death in two-thirds of cases.

Publication types

  • Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Databases, Factual
  • Humans
  • Intracranial Hemorrhages / chemically induced*
  • Intracranial Hemorrhages / mortality
  • Neoplasms / drug therapy*
  • Risk Factors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab