title: 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.
authors.affiliation: Neuro-Oncology Service, Division of Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann St., 64239, Tel-Aviv, Israel. deborahblumenthal@gmail.com.
authors.forename: D T
authors.initials: DT
authors.lastname: Blumenthal
authors.affiliation: Omnistat Statistical Consulting, Tel-Aviv, Israel.
authors.forename: L
authors.initials: L
authors.lastname: Mendel
authors.affiliation: Neuro-Oncology Service, Division of Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann St., 64239, Tel-Aviv, Israel.
authors.forename: F
authors.initials: F
authors.lastname: Bokstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D016190:Carboplatin; D002166:Camptothecin
keywords: Bevacizumab; Chemotherapy; Dose; Glioblastoma; Recurrent; Regimen; Standard; Toxicity