Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma.

BACKGROUND: The effectiveness of stereotactic radiosurgery (SRS) for recurrent glioblastoma (rGBM) remains uncertain. SRS has been associated with a high risk of radionecrosis in gliomas. OBJECTIVE: To determine the safety of dose escalation of single-fraction radiosurgery for rGBM in the setting of bevacizumab therapy. METHODS: We conducted a prospective trial to determine the safety and synergistic benefit of higher doses of SRS administered with bevacizumab for rGBM. A single dose of bevacizumab was given prior to SRS and continued until progression. Dose-limiting toxicity was evaluated in successive cohorts of 3 patients. RESULTS : Seven males and 2 females entered the study. The maximum linear diameter of the enhancing tumor was 2.58 cm (2.04-3.09). Prescription dose was escalated from 18 to 22 Gy. The radiosurgery target was chosen before the first dose of bevacizumab, about 1 wk prior to SRS treatment. Pre-SRS bevacizumab treatment was associated with a reduction of the mean volume of the enhancing lesion from 4.7 to 2.86 cm(3) on the day of SRS (P = 103). No patient developed an acute side effect related to SRS treatment. The combination of SRS and bevacizumab resulted in a partial response in 3 patients and stable disease in 6 patients. Median progression-free and overall survival were 7.5 and 13 mo, respectively. CONCLUSION : A single dose of bevacizumab prior to SRS permitted safe prescription dose escalation up to 22 Gy for rGBM. Further evaluation of the efficacy of SRS for rGBM should be performed in the setting of bevacizumab treatment.