A pilot study of bevacizumab and stereotactic intensity modulated re-irradiation for recurrent high grade gliomas

Abstract

2028 Background: Bevacizumab is a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A). Preclinical studies suggest that inhibition of VEGF-A improves glioma response to radiotherapy. The concurrent use of bevacizumab and cranial radiotherapy has not been investigated. The objective of this study is to determine the safety of this combination. Methods: Patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytomas (AA) less than 3.5 cm received bevacizumab (10 mg/kg IV) every 2 weeks. MRI after cycle 1 (28 days) was done to reassess response and for RT planning. Patients then received stereotactic intensity modulated radiation therapy (IMRT): 30Gy in 5 fractions over 15 days. Bevacizumab treatment, given every 2 weeks, was administered during radiotherapy and continued until tumor progression. Brain MRI to assess response was performed after odd cycles. MR T1 and T2* perfusion were performed at baseline and after cycle 1. Results: 12 patients (10 GBM, 2 AA) with median age 53 (range, 30–61) and median KPS 90 (range, 80–100) received a median of 5.5 cycles of bevacizumab. In 1 patient, stereotactic IMRT could not be delivered safely to tumor. Grade III events occurred in 10 patients including hypertension, headache, seizures, neutropenia, hyponatremia and hypophosphatemia. There were no grade IV or V events, no dose limiting toxicities and no intracranial hemorrhage. 7/12 patients had objective responses (3 CR and 4 PR). In 5, SD was the best reported response. At last follow up, ten patients remain on study; 2 have come off for PD. Estimated 6 month PFS is 76%. MR perfusion imaging demonstrated a decrease in mean perfusion values after 1 cycle of bevacizumab. Conclusions: Bevacizumab in combination with RT is safe and well tolerated. Imaging responses and duration of disease control suggest that this regimen is active in this subset of recurrent glioma patients. Further investigations to determine efficacy and possible synergy of bevacizumab with radiotherapy are warranted. [Table: see text]