Originally published as JCO Early Release 10.1200/JCO.2008.16.3055 on December 29 2008

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Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma

From the Neuro-Oncology Branch, Radiation Oncology Branch and Biometric Branch, National Cancer Institute; Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke; and the Department of Radiology, the Clinical Center, National Institutes of Health, Bethesda, MD.

Corresponding author: Howard A. Fine, MD, National Institutes of Health, 9030 Old Georgetown Rd, Bloch Bldg 82, Room 235, MSC 8200, Bethesda, MD 20892-8200; e-mail: hfine{at}mail.nih.gov.

Purpose To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.

Patients and Methods Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m² or 125 mg/m² every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks.

Results Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days.

Conclusion We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.

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

Clinical Trials repository link available on JCO.org.

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