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).

Conclusion: 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

Written by:
Klotz L, Drachenberg D, Singal R, Aprikian A, Fradet Y, Kebabdjian M, Zarenda M, Chin J.   Are you the author?
Sunnybrook Health Sciences Centre, Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Reference: Prostate Cancer Prostatic Dis. 2014 Sep 2. Epub ahead of print.
doi: 10.1038/pcan.2014.24


PubMed Abstract
PMID: 25179591

UroToday.com Prostate Cancer Section

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