title: Phase II Trial of Upfront Bevacizumab, Irinotecan, and Temozolomide for Unresectable Glioblastoma.
abstract: CONCLUSIONS
  Trials focusing on unresectable multifocal glioblastoma are needed because of the extremely poor prognosis and challenges in receiving standard therapy, such as concurrent radiation and chemotherapy.Developing a strategy to chemically debulk tumors before radiation and/or surgery is warranted.
  
  
  BACKGROUND
  Extent of resection remains a key prognostic factor in glioblastoma (GBM), with gross total resection providing a better prognosis than biopsy or subtotal resection. We conducted a phase II trial of upfront therapy with bevacizumab (BV), irinotecan (CPT-11), and temozolomide (TMZ) prior to chemoradiation in patients with unresectable, subtotally resected, and/or multifocal GBM.
  
  
  METHODS
  Patients received up to 4 cycles of TMZ at 200 mg/m(2) per day on days 1-5 (standard dosing) and BV at 10 mg/kg every 2 weeks on a 28-day cycle. CPT-11 was given every 2 weeks on a 28-day cycle at 125 mg/m(2) or 340 mg/m(2) depending on antiepileptic drugs. Magnetic resonance imaging of the brain was done every 4 weeks, and treatment continued as long as there was no tumor progression or unmanageable toxicity. The primary endpoint was tumor response rate, with a goal of 26% or greater.
  
  
  RESULTS
  Forty-one patients were enrolled from December 2009 to November 2010. Radiographic responses were as follows: 9 patients (22.0%) had partial response, 25 (61.0%) had stable disease, and 2 (4.9%) had progression; 5 patients were not assessed. Cumulative response rate was 22%. Median overall survival was 12 months (95% confidence interval: 7.2-13.5 months).
  
  
  CONCLUSIONS
  Upfront treatment with BV, TMZ, and CPT-11 is tolerable and can lead to radiographic response in unresectable and/or subtotally resected GBM.
authors.affiliation: Departments of Neurology, katherine.peters@duke.edu.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA;
authors.forename: Emil
authors.initials: E
authors.lastname: Lou
authors.affiliation: Departments of Neurology.
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.affiliation: Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, USA;
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.affiliation: Surgery.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lipp
authors.affiliation: Surgery.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
authors.affiliation: Biostatistics, and.
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.affiliation: Biostatistics, and.
authors.forename: Frances
authors.initials: F
authors.lastname: McSherry
authors.affiliation: Medicine, Duke University Medical Center, Durham, North Carolina, USA;
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.affiliation: Division of Medical Oncology, St. Francis Medical Cancer Center, Hartford, Connecticut, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide