Prostate Cancer An Open, Randomised, Multicentre, Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients Davide Bedognetti a , Alessandra Rubagotti a,b , Giario Conti c , Francesco Francesca d , Ottavio De Cobelli e , Luca Canclini f , Michele Gallucci g , Francesco Aragona h , Pasquale Di Tonno i , Pietro Cortellini j , Giuseppe Martorana k , Alberto Lapini l , Francesco Boccardo a,b, * a University of Genoa, Genoa, Italy b National Cancer Research Institute of Genoa, Genoa, Italy c S. Anna Hospital, Como, Italy d S. Chiara Hospital, Pisa, Italy e European Institute of Oncology, Milan, Italy f Bergamo Hospital, Bergamo, Italy g Regina Elena Cancer Institute, Rome, Italy h Cannizzaro Hospital, Catania, Italy i University of Bari, Bari, Italy j General Hospital, Parma, Italy k University of Bologna, Bologna, Italy l University and Carreggi Hospital, Florence, Italy EUROPEAN UROLOGY 57 (2010) 238–245 available at www.sciencedirect.com journal homepage: www.europeanurology.com Article info Article history: Accepted May 7, 2009 Published online ahead of print on May 19, 2009 Keywords: Gynaecomastia Mastalgia Sexual functioning Prostate cancer Tamoxifen Bicalutamide Abstract Background: Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynae- comastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interfer- ence between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration. Objective: To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated. Design, setting, and participants: This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n = 41) and weekly (n = 39). Median follow-up was 24.2 mo. Intervention: Daily bicalutamide (150 mg) plus daily tamoxifen 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events. * Corresponding author. University and National Cancer Research Institute, Largo R. Benzi 10, 16132 Genoa, Italy. Tel. +39 0105600560; Fax: +39 010352753. E-mail address: f.boccardo@unige.it (F. Boccardo). 0302-2838/$ – see back matter # European Association of Urology Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2009.05.019