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Clinical Research

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

Prostate Cancer and Prostatic Diseases volume 17, pages 320–324 (2014)Cite this article

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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.

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

    L Klotz, D Drachenberg, R Singal, A Aprikian, Y Fradet, M Kebabdjian, M Zarenda & J Chin

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  1. L Klotz
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Correspondence to L Klotz.

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This study was funded by an unrestricted grant from AstraZeneca Canada. The authors declare no conflict of interest.

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Klotz, L., Drachenberg, D., Singal, R. et al. 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. Prostate Cancer Prostatic Dis 17, 320–324 (2014). https://doi.org/10.1038/pcan.2014.24

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