title: High-dose bevacizumab in the treatment of patients with advanced clear cell renal carcinoma: a phase II trial of the Sarah Cannon Oncology Research Consortium.
abstract: BACKGROUND
  The dose of bevacizumab necessary to optimally inhibit tumor angiogenesis in advanced renal cell carcinoma is unknown. In this phase II trial, we evaluated the efficacy and safety of 2 escalated doses of bevacizumab in patients with advanced clear cell renal carcinoma.
  
  
  METHODS
  Eligible patients had metastatic or locally advanced unresectable clear cell renal carcinoma. Patients who were previously untreated or who had previously received vascular endothelial growth factor receptor (VEGFR)-targeted therapy were eligible and were considered separately in the efficacy evaluation. Two doses of bevacizumab were evaluated in sequential cohorts: 15 mg/kg every 2 weeks and 15 mg/kg weekly. The initial reevaluation was at 8 weeks; responding and stable patients continued treatment, with reevaluations every 8 weeks until tumor progression or unacceptable toxicity occurred.
  
  
  RESULTS
  One hundred nineteen eligible patients were enrolled and received bevacizumab 15 mg/kg every 2 weeks (n = 61) or bevacizumab 15 mg/kg weekly (n = 58). Seventy patients were previously untreated with VEGFR-targeted therapy. In previously untreated patients, the overall response rate was 19%, with a median progression-free survival (PFS) of 7.8 months. Less activity was seen in patients previously treated with VEGFR-targeted agents (overall response rate, 4%; median PFS, 3.7 months). There was no suggestion of any difference in efficacy between the 2 dose levels tested. Both dose levels were tolerated well by most patients, with a spectrum of toxicity typical for bevacizumab. Grade 3/4 proteinuria was more frequent with both of these escalated doses, particularly with 15 mg/kg weekly.
  
  
  CONCLUSIONS
  Although administration of escalated doses of bevacizumab was feasible in patients with advanced clear cell renal carcinoma, there was no suggestion that these doses were more efficacious than bevacizumab administered at the standard dose of 10 mg/kg every 2 weeks.
authors.affiliation: Sarah Cannon Research Institute, 3322 West End Ave., Nashville, TN 37203, USA. aso@scresearch.net
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Shipley
authors.forename: James
authors.initials: J
authors.lastname: Reeves
authors.forename: Edward R
authors.initials: ER
authors.lastname: Arrowsmith
authors.forename: Edward K
authors.initials: EK
authors.lastname: Barnes
authors.forename: David M
authors.initials: DM
authors.lastname: Waterhouse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Clear cell; Phase II; Renal carcinoma