title: A phase 2 trial of single-agent bevacizumab given in an every-3-week schedule for patients with recurrent high-grade gliomas.
abstract: BACKGROUND
  The authors evaluated a 3-week schedule of bevacizumab in patients with recurrent high-grade glioma (HGG).
  
  
  METHODS
  Patients received bevacizumab 15 mg/kg every 3 weeks and were evaluated every 6 weeks until tumor progression. Tissue correlates were used to quantify tumor content of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor-2 (VEGFR2).
  
  
  RESULTS
  Of 61 patients who were treated (35 men and 26 women; median age, 52 years; age range, 21-78 years), 50 patients had glioblastoma multiforme (GBM), and 11 patients had anaplastic glioma (AG). The median number of previous chemotherapies was 2 (range, 1-5 previous chemotherapies), and 16 patients had received ≥3 previous chemotherapies. The median number of bevacizumab doses was 4 (range, 1-20 doses), and 45% of patients received >5 doses. The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. One grade 2 intratumoral bleed and 1 bowel perforation were reported. For patients with GBM, the 6-month progression-free survival rate was 25%, the median time to tumor progression was 10.8 weeks, and the median overall survival was 25.6 weeks. The best response included a partial response in 15 patients (24.5%) and stable disease in 31 patients (50.8%) patients; radiographic recurrence patterns included increased changes in fluid attenuation inversion recovery (24%) and multifocal recurrence (20%). The median survival after bevacizumab failure was 10 weeks. The ratio of tumor VEGFA/VEGFR2 was increased in patients aged >55 years; an increased VEGFA/VEGFR2 ratio was correlated nonsignificantly with decreased survival (P = .052).
  
  
  CONCLUSIONS
  An every-3-week schedule of bevacizumab had antitumor activity and was relatively nontoxic for patients with recurrent HGG. The predictive value of VEGFA/VEGFR2 in tumor will require validation in a larger patient cohort.
authors.affiliation: Department of Neurology, Northwestern University, Chicago, IL, USA. jraizer@nmff.org
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Raizer
authors.forename: Sean
authors.initials: S
authors.lastname: Grimm
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Nicholas
authors.forename: James P
authors.initials: JP
authors.lastname: Chandler
authors.forename: Kenji
authors.initials: K
authors.lastname: Muro
authors.forename: Steven
authors.initials: S
authors.lastname: Dubner
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Rademaker
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Renfrow
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040301:Vascular Endothelial Growth Factor Receptor-2