Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

Abstract

Purpose Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of the concurrent use of bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg IV) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in 5 fractions after the first cycle of bevacizumab. Results Twenty-five patients (20 GBM and 5 AG) median age of 56 years (range, 30 to 80) and median KPS 90 (range, 70 to 100) received a median of 7 cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment due to: grade 3 CNS intratumoral hemorrhage, wound dehiscence and bowel perforation. Other non-hematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously-irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression free survival was 65%; median overall survival was 12.5 months and 1-year survival was 54%. Discussion Bevacizumab in combination with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control and survival suggest that this regimen is active in recurrent malignant glioma.