title: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.
abstract: OBJECTIVE
  The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan.
  
  
  METHODS
  This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging.
  
  
  RESULTS
  The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli).
  
  
  CONCLUSIONS
  Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.
authors.affiliation: Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA. vrede001@mc.duke.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marcello
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Quinn
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Sith
authors.initials: S
authors.lastname: Sathornsumetee
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: John
authors.initials: J
authors.lastname: Sampson
authors.forename: Melissa
authors.initials: M
authors.lastname: Wagner
authors.forename: Leighann
authors.initials: L
authors.lastname: Bailey
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin