title: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma.
abstract: OBJECTIVE
  To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma.
  
  
  METHODS
  Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks. After tumor progression, patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2) or 125 mg/m(2) every 2 weeks, depending on use of enzyme-inducing antiepileptic drugs. Complete patient evaluations were repeated every 4 weeks.
  
  
  RESULTS
  Forty-eight heavily pretreated patients were accrued to this study. Thromboembolic events (12.5%), hypertension (12.5%), hypophosphatemia (6%), and thrombocytopenia (6%) were the most common drug-associated adverse events. Six patients (12.5%) were removed from study for drug-associated toxicity (five thromboembolic events, one bowel perforation). Thirty-four patients (71%) and 17 patients (35%) achieved radiographic response based on Levin and Macdonald criteria, respectively. Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%). The 6-month overall survival was 57% (95% CI, 44% to 75%). Median overall survival was 31 weeks (95% CI, 21 to 54 weeks). Early magnetic resonance imaging response (first 96 hours and 4 weeks) was predictive of long-term PFS, with the Levin criteria being more predictive than Macdonald criteria. Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses. Eighteen patients (95%) experienced disease progression by the second cycle, and the median PFS was 30 days.
  
  
  CONCLUSIONS
  We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma.
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-8200, USA.
authors.forename: Teri N
authors.initials: TN
authors.lastname: Kreisl
authors.forename: Lyndon
authors.initials: L
authors.lastname: Kim
authors.forename: Kraig
authors.initials: K
authors.lastname: Moore
authors.forename: Paul
authors.initials: P
authors.lastname: Duic
authors.forename: Cheryl
authors.initials: C
authors.lastname: Royce
authors.forename: Irene
authors.initials: I
authors.lastname: Stroud
authors.forename: Nancy
authors.initials: N
authors.lastname: Garren
authors.forename: Megan
authors.initials: M
authors.lastname: Mackey
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: John
authors.initials: J
authors.lastname: Park
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin