The optimal regimen of bevacizumab for recurrent glioblastoma: does dose matter?

Abstract

The FDA-approved schedule and dose of bevacizumab (BVZ) for recurrent glioblastoma (rGB) (10 mg/kg q 2 weeks) were adopted from systemic cancer protocols. No dose-defining studies have been performed for glioblastoma. We began using BVZ for the treatment of rGB in 2005 at the dose of 5 mg/kg every 2 weeks combined with irinotecan, and later as single agent. Our previous report of 20 patients treated with BVZ 5 mg/kg every 2 weeks showed similar response rates and overall survival (OS) compared to other BVZ treatment protocols, with less adverse effects. In this study we retrospectively reviewed our 7 year experience with BVZ in 162 rGB patients. Treatment outcomes were analyzed from 87 patients who received BVZ at 5 mg/kg and 75 patients at 10 mg/kg. While median age was similar in both groups, the median KPS was significantly higher in the group treated with 10 mg/kg BVZ (85 versus 60). There was no significant difference in OS or progression free survival (PFS) between the groups treated with BVZ 5 versus 10 mg/kg. Overall survival was significantly improved in the subgroup treated with cytotoxic therapy in addition to BVZ 10 mg/kg. There were more adverse events seen with BVZ 10 mg/kg. There is no significant difference in OS for rGB treated with BVZ 5 mg/kg versus 10 mg/kg when given as monotherapy. The smaller dose was slightly less toxic. Addition of cytotoxic therapy resulted in prolongation of OS in a small subgroup of BVZ 10 mg/kg.

Keywords: Bevacizumab; Chemotherapy; Dose; Glioblastoma; Recurrent; Regimen; Standard; Toxicity.