Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.
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.
Reardon
David A
DA
Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710, USA. reard003@mc.duke.edu
Desjardins
Annick
A
Peters
Katherine
K
Gururangan
Sridharan
S
Sampson
John
J
Rich
Jeremy N
JN
McLendon
Roger
R
Herndon
James E
JE
Marcello
Jennifer
J
Threatt
Stevie
S
Friedman
Allan H
AH
Vredenburgh
James J
JJ
Friedman
Henry S
HS
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005047:Etoposide; D003606:Dacarbazine; D000077204:Temozolomide