Bevacizumab in combination with radiotherapy and temozolomide for patients with newly diagnosed glioblastomamultiforme

Background. Patients with a newly diagnosed glioblastoma multiforme (GBM) have a high risk of recurrent disease with a dismal outcome despite intensive treatment of sequential surgery and chemoradiotherapy with temozolomide (TMZ), followed by TMZ as a single agent. Bevacizumab (BV) may increase response rates to chemotherapy in the recurrent treatment setting of GBM. We hypothesized that a neoadjuvant treatment strategy for patients with newly diagnosed GBM using chemoradiotherapy plus BV would improve resectability and thus survival. We performed a phase II trial of the treatment strategy of BV plus chemoradiation to determine the safety of this combination in patients who had already undergone primary surgery for their GBM. Methods. After a biopsy (6 patients) or a resection (13 patients) of a newly diagnosed GBM, 19 patients received radiotherapy (30 fractions of 2 Gy) in combinationwith daily TMZ 75 mg/m2 and BV 10 mg/kg on days 1, 14, and 28, followed by 6monthly cycles ofTMZ150-200mg/m2ondays 1-5. Results. The overall response rate was 26%.Three patients had a complete response after resection, and in two patients, a complete response after resection followed by chemoradiation plus BV was seen. No grade 3-4 toxicities were observed during combination treatment. The median progression-free survival was 9.6 months (95% confidence interval [CI]: 4.3-14.4 months). The median overall survival was16months(95%CI: 8.1-26.3 months), similar to amatched control groupthat received standardchemoradiotherapy from our institution. Conclusion. Combination of bevacizumab with radiotherapy and TMZis safe and feasible in patientswith newly diagnosed GBM, but because of low response rates, this treatment strategydoesnot favor a neoadjuvant approach.