title: An open-label, phase 2 trial of bicalutamide dose escalation from 50 mg to 150 mg in men with CAB and castration resistance. A Canadian Urology Research Consortium Study.
abstract: BACKGROUND
  Bicalutamide is a widely used, relatively non-toxic anti-androgen, particularly when used in combination with androgen deprivation. In men on combined androgen blockade (CAB), the typical dose is 50 mg per day. For men receiving monotherapy with bicalutamide anti-androgen, the dose is 150 mg per day. The objective was to determine the PSA response rate to increasing bicalutamide to 150 mg per day in men who develop castrate-resistant prostate cancer (CRPC) on CAB with goserelin acetate and bicalutamide 50 mg per day.
  
  
  METHODS
  A national, multicentre, phase 2, open-label study in men on CAB with a rising PSA>2.0. The primary end point of the trial was PSA response at 12 months, defined as a decline by 50% or more compared with baseline value. Partial response was defined as a PSA decline of 10-49%. Secondary end points were duration of PSA response, change in slope of serum PSA, change in ratio of free PSA: total PSA at 3 months, 6 months and 12 months as compared with baseline; duration of the bicalutamide withdrawal response after discontinuation; the rate of cardiovascular events; and toxicity. The study was initially planned to accrue 100 patients, but was closed early due to diminishing accrual.
  
  
  RESULTS
  Sixty-four patients were accrued; 61 patients received trial treatment and constituted the intention-to-treat (ITT) cohort. 70% were M0. Among 59 evaluable ITT patients, 13 (22%) patients had a >50% PSA decline, 5 (8%) had a decline between 10 and 50%, 4 (7%) had stabilization and 37 (63%) had PSA progression. The median duration was 3.7 months (95% confidence interval of 0.92-6.21 months).
  
  
  CONCLUSIONS
  In patients with early biochemical failure on CAB with bicalutamide 50 mg, an increase in dose to 150 mg of bicalutamide resulted in a PSA response of ⩾ 50% in 22% of patients. Toxicity was mild. Bicalutamide dose intensification may benefit a subset of patients with CRPC. We believe this relatively inexpensive approach warrants further evaluation.
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Klotz
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Drachenberg
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Singal
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Aprikian
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Fradet
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Kebabdjian
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Zarenda
authors.affiliation: Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Chin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects; D002170:Canada; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014105:Tosyl Compounds / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D017430:Prostate-Specific Antigen