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.

Extended field stereotactic radiosurgery for recurrent glioblastoma

“…Obviously, radiation therapy, including SRS, and temozolomide are not sufficient to control the disease. New approaches are underway, including monoclonal antibodies that target specific molecules, for example, bevacizumab, 31,32 and oncolytic viruses that replicate selectively in tumor cells. 33 In conclusion, extended field SRS was well tolerated and superior to conventional SRS in the local control of small recurrent lesions of glioblastoma, although a further device to suppress remote recurrences may be necessary to improve survival.…”

Bevacizumab plus Radiotherapy–Temozolomide for Newly Diagnosed Glioblastoma

“…16 The results of phase 1/2 studies support a role for the anti-VEGF-A molecule bevacizumab in recurrent and newly diagnosed glioblastoma. [17][18][19][20][21][22] We report the results of a phase 3 trial of bevacizumab plus radiotherapy-temozolomide as compared with placebo plus radiotherapytemozolomide in patients with newly diagnosed glioblastoma.…”

Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control With No Radiation Necrosis: Promising Results in the Management of Patients With Small Recurrent Inoperable GBM

“…In the present study, 15/21 patients (71.4%) received chemotherapy tailored to their condition while undergoing HFSRT, and there were no incidences of RN or CTC/RTOG toxicities > Grade 2. While the use of bevacizumab has been reported to suppress RN [37], 10/21 patients in the present series did not receive bevacizumab. Furthermore, of the patients dependent on steroid use prior to HFSRT, 54% experienced a decrease in steroid dose after HFSRT.…”