title: Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.
abstract: We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received bevacizumab (10 mg/kg) every 2 weeks with either oral etoposide (50 mg/m2) daily for 21 consecutive days each month or daily temozolomide (50 mg/m2). The primary endpoint was 6-month progression-free survival (PFS-6) and secondary endpoints included safety and overall survival. Both the etoposide and temozolomide arms of the study closed at the interim analysis due to lack of adequate anti-tumor activity. No radiographic responses were observed. Although 12 patients (52%) achieved stable disease, PFS-6 was 4.4% and the median PFS was 7.3 weeks. The only grade 4 adverse event was reversible neutropenia. Grade 3 toxicities included fatigue (n = 2) and infection (n = 1). Metronomic etoposide or temozolomide is ineffective when administered with bevacizumab among recurrent GBM patients who have progressed on prior bevacizumab therapy. Alternative treatment strategies remain critically needed for this indication.
authors.affiliation: Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710, USA. reard003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: Katherine
authors.initials: K
authors.lastname: Peters
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: John
authors.initials: J
authors.lastname: Sampson
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marcello
authors.forename: Stevie
authors.initials: S
authors.lastname: Threatt
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D000077204:Temozolomide
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005047:Etoposide; D003606:Dacarbazine; D000077204:Temozolomide