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Clinical Trial
. 2009 Feb 10;27(5):740-5.
doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29.

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma

Teri N Kreisl  1 , Lyndon Kim, Kraig Moore, Paul Duic, Cheryl Royce, Irene Stroud, Nancy Garren, Megan Mackey, John A Butman, Kevin Camphausen, John Park, Paul S Albert, Howard A Fine
Affiliations
Clinical Trial

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma

Teri N Kreisl et al. J Clin Oncol. .

Abstract

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/m(2) or 125 mg/m(2) 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.

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Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
(A) Progression-free survival (PFS) with point-wise 95% CIs (dotted lines). The 9-week PFS is 74% (95% CI, 62% to 89%). The 6-month PFS is 29% (95% CI, 18% to 48%). The median PFS is 16 weeks (95% CI, 12 to 26 weeks). (B) Overall survival with point-wise 95% CIs (dotted lines). The 6-month OS is 57% (95% CI, 44% to 75%). The median OS is 31 weeks (95% CI, 21 to 54 weeks).
Fig 2.
Fig 2.
Magnetic resonance imaging (MRI)–documented response to bevacizumab. (A) Pretreatment MRI scan for patient 1. (B) Post-treatment MRI scan for patient 1 after 3 months of bevacizumab without concomitant corticosteroid therapy. (C) Pretreatment MRI scan for patient 2. (D) Post-treatment MRI scan for patient 2 showing a partial response by Levin criteria versus stable disease by cross-sectional diameters (Macdonald criteria).
Fig 3.
Fig 3.
(A) Progression-free survival based on 4-week magnetic resonance imaging (MRI) response (Macdonald criteria). Patients with partial response (PR; top curve) versus stable disease (SD; bottom curve). Log-rank test (two-sided) P = .07. (B) Progression-free survival based on 4-week MRI response (Levin criteria). Patients with PR (top curve) versus SD (bottom curve). Log-rank test (two-sided) P = .03.
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