title: Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401.
abstract: OBJECTIVE
  A randomized, placebo-controlled study based on preclinical and clinical data that supports the potential role of vascular endothelial growth factor in prostate cancer was performed to evaluate the addition of bevacizumab to standard docetaxel and prednisone therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).
  
  
  METHODS
  Patients with chemotherapy-naive progressive mCRPC with Eastern Cooperative Oncology Group performance status ≤ 2 and adequate bone marrow, hepatic, and renal function were randomly assigned to receive docetaxel 75 mg/m(2) intravenously (IV) over 1 hour for 21 days plus prednisone 5 mg orally twice per day (DP) with either bevacizumab 15 mg/kg IV every 3 weeks (DP + B) or placebo. The primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), 50% decline in prostate-specific antigen, objective response (OR), and toxicity.
  
  
  RESULTS
  In total, 1,050 patients were randomly assigned. The median OS for patients given DP + B was 22.6 months compared with 21.5 months for patients treated with DP (hazard ratio, 0.91; 95% CI, 0.78 to 1.05; stratified log-rank P = .181). The median PFS time was superior in the DP + B arm (9.9 v 7.5 months, stratified log-rank P < .001) as was the proportion of patients with OR (49.4% v 35.5%; P = .0013). Grade 3 or greater treatment-related toxicity was more common with DP + B (75.4% v 56.2%; P ≤ .001), as was the number of treatment-related deaths (4.0% v 1.2%; P = .005).
  
  
  CONCLUSIONS
  Despite an improvement in PFS and OR, the addition of bevacizumab to docetaxel and prednisone did not improve OS in men with mCRPC and was associated with greater toxicity.
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA. wm.kevin.kelly@jefferson.edu
authors.forename: William Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Michael
authors.initials: M
authors.lastname: Carducci
authors.forename: Daniel
authors.initials: D
authors.lastname: George
authors.forename: John F
authors.initials: JF
authors.lastname: Mahoney
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.forename: J Paul
authors.initials: JP
authors.lastname: Monk
authors.forename: Ellen
authors.initials: E
authors.lastname: Kaplan
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D019008:Drug Resistance, Neoplasm; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010919:Placebos; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000726:Androgen Antagonists; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D017430:Prostate-Specific Antigen; D011241:Prednisone