Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma.

Abstract

PURPOSE:

Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma.

EXPERIMENTAL DESIGN:

We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma. Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded. Patients were scheduled to receive bevacizumab and irinotecan i.v. every 2 weeks of a 6-week cycle. Bevacizumab was administered at 10 mg/kg. The dose of irinotecan was determined based on antiepileptic use: patients taking enzyme-inducing antiepileptic drugs received 340 mg/m(2), whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m(2). Toxicity and response were assessed.

RESULTS:

Thirty-two patients were assessed (23 with grade IV glioma and 9 with grade III glioma). Radiographic responses were noted in 63% (20 of 32) of patients (14 of 23 grade IV patients and 6 of 9 grade III patients). The median progression-free survival was 23 weeks for all patients (95% confidence interval, 15-30 weeks; 20 weeks for grade IV patients and 30 weeks for grade III patients). The 6-month progression-free survival probability was 38% and the 6-month overall survival probability was 72%. No central nervous system hemorrhages occurred, but three patients developed deep venous thromboses or pulmonary emboli, and one patient had an arterial ischemic stroke.

CONCLUSIONS:

The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.

• Authors: James J Vredenburgh, Annick Desjardins, James E Herndon 2nd, Jeannette M Dowell, David A Reardon, Jennifer A Quinn, Jeremy N Rich, Sith Sathornsumetee, Sridharan Gururangan, Melissa Wagner, Darell D Bigner, Allan H Friedman, Henry S Friedman
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 4 Pg. 1253-9 (Feb 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17317837 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Irinotecan
• Camptothecin

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bevacizumab
• Brain Neoplasms (drug therapy)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Female
• Glioma (drug therapy)
• Humans
• Irinotecan
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Prospective Studies