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Bevacizumab Plus Irinotecan in Recurrent Glioblastoma Multiforme

James J. Vredenburgh, Annick Desjardins, James E. Herndon, II, Jennifer Marcello, David A. Reardon, Jennifer A. Quinn, Jeremy N. Rich, Sith Sathornsumetee, Sridharan Gururangan, John Sampson, Melissa Wagner, Leighann Bailey, Darell D. Bigner, Allan H. Friedman, Henry S. Friedman

From the Preston Robert Tisch Brain Tumor Center; and the Departments of Surgery, Medicine, Biostatistics, Pediatrics, Neurobiology, and Pathology, Duke University Medical Center, Durham, NC

Address reprint requests to James J. Vredenburgh, MD, Duke University Medical Center, Box 3624, Durham, NC 27710; e-mail: vrede001{at}mc.duke.edu

Purpose: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan.

Patients and Methods: This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m², and patients not taking EIAEDs received 125 mg/m². After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging.

Results: The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli).

Conclusion: Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.

Supported by Grants No. 5 P50 CA108786, 5 P50 NS20023, and 4 R37 CA11898 from the National Institutes of Health, Department of Health and Human Services, Bethesda, MD; the Preston Robert Tisch Brain Tumor Research Fund; and the Bryan Cless Research Fund. J.N.R. is a Damon Runyon-Lilly Clinical Investigator.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Editorial

• Taming Glioblastoma: Targeting Angiogenesis
  Eric T. Wong and Steven Brem
  JCO 2007 25: 4705-4706 [Full Text]

Related Correspondence

• Bevacizumab Plus Irinotecan in Recurrent Glioblastoma
  Marc C. Chamberlain
  JCO 2008 26: 1012-1013 [Full Text]

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