Bevacizumab and irinotecan therapy in glioblastoma multiforme: a series of 13 cases

J Neurosurg. 2008 Aug;109(2):268-72. doi: 10.3171/JNS/2008/109/8/0268.

Abstract

Object: Endothelial proliferation has been recognized as a marker of high-grade or aggressive glioma. Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan. The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan.

Methods: Standard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients. The median number of therapies applied, including initial surgery, was 5 (range 3-7 therapies). Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks. Four patients received bevacizumab at a dose of 10 mg/m2; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks.

Results: Of the 13 treated patients, 10 (77%) had a radiologically demonstrated partial response and 3 (23%) had stable disease. Six patients (46%) had a clinical response. The median time to disease progression while on treatment was 24 weeks. The median overall survival was 27 weeks. The disease progressed in 8 patients, despite an initial response. Five patients are still responding to therapy. Six of the 8 patients whose disease progressed have died. Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding.

Conclusions: The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed, heavily pretreated population of patients with high-grade malignant glioma, most of whom would not be candidates for clinical trials.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Bevacizumab
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / surgery
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Combined Modality Therapy
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / radiotherapy
  • Glioblastoma / surgery
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / radiotherapy
  • Neoplasm Recurrence, Local / surgery
  • Survival Rate
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Phytogenic
  • Bevacizumab
  • Irinotecan
  • Camptothecin