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, Alessandra Rubagotti, Giario Conti, Francesco Francesca, Ottavio De Cobelli, Luca Canclini, Michele Gallucci, Francesco Aragona, Pasquale Di Tonno, Pietro Cortellini, Giuseppe Martorana, Alberto Lapini, Francesco Boccardo

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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 gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference 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. Measurements: For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires. Results and limitations: Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen (p = 0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p = 0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far. Conclusions: This study demonstrated that tamoxifen 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.

Original languageEnglish
Pages (from-to)238-245
Number of pages8
JournalEuropean Urology
Volume57
Issue number2
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

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Keywords

  • Bicalutamide
  • Gynaecomastia
  • Mastalgia
  • Prostate cancer
  • Sexual functioning
  • Tamoxifen

ASJC Scopus subject areas

  • Urology

Cite this

Bedognetti, D., Rubagotti, A., Conti, G., Francesca, F., De Cobelli, O., Canclini, L., Gallucci, M., Aragona, F., Di Tonno, P., Cortellini, P., Martorana, G., Lapini, A., & Boccardo, F. (2010). 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. European Urology, 57(2), 238-245. https://doi.org/10.1016/j.eururo.2009.05.019