title: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma.
abstract: OBJECTIVE
  We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial.
  
  
  METHODS
  One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review. Secondary end points included safety and overall survival.
  
  
  RESULTS
  In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups, estimated 6-month progression-free survival rates were 42.6% and 50.3%, respectively; objective response rates were 28.2% and 37.8%, respectively; and median overall survival times were 9.2 months and 8.7 months, respectively. There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time. Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan, 46.4% and 65.8%, respectively, experienced grade > or = 3 adverse events, the most common of which were hypertension (8.3%) and convulsion (6.0%) in the bevacizumab-alone group and convulsion (13.9%), neutropenia (8.9%), and fatigue (8.9%) in the bevacizumab-plus-irinotecan group. Intracranial hemorrhage was noted in two patients (2.4%) in the bevacizumab-alone group (grade 1) and in three patients (3.8%) patients in the bevacizumab-plus-irinotecan group (grades 1, 2, and 4, respectively).
  
  
  CONCLUSIONS
  Bevacizumab, alone or in combination with irinotecan, was well tolerated and active in recurrent glioblastoma.
authors.affiliation: Brain Tumor Center, Duke University, Durham, NC 27710, USA. fried003@mc.duke.edu
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Nina
authors.initials: N
authors.lastname: Paleologos
authors.forename: Martin K
authors.initials: MK
authors.lastname: Nicholas
authors.forename: Randy
authors.initials: R
authors.lastname: Jensen
authors.forename: James
authors.initials: J
authors.lastname: Vredenburgh
authors.forename: Jane
authors.initials: J
authors.lastname: Huang
authors.forename: Maoxia
authors.initials: M
authors.lastname: Zheng
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin