A randomized trial comparing tamoxifen therapy vs. tamoxifen prophylaxis in bicalutamide-induced gynecomastia

Clin Genitourin Cancer. 2012 Sep;10(3):174-9. doi: 10.1016/j.clgc.2012.03.002. Epub 2012 Apr 12.


Background: Tamoxifen (TAM) has been shown to be active against the bicalutamide-induced breast events (BEs) gynecomastia, and breast pain in patients with prostate cancer (PC). Optimal doses and schedules are not yet established. Debate still exists about whether prophylaxis with TAM is more effective than treatment of BEs when diagnosed. The results of a randomized study comparing TAM prophylaxis vs. TAM therapy are presented.

Methods: One hundred seventy-six patients with prostate cancer (PC) who were candidates for bicalutamide monotherapy were randomized to receive TAM 20 mg daily orally within 1 month from the onset of BEs (arm A) vs. TAM 10 mg daily starting simultaneously with bicalutamide (arm B). TAM was administered for up to 1 year. BEs were evaluated by a self-administered visual analogue scale. Neither ultrasonography nor calipers were used to measure the degree of gynecomastia.

Results: In arm A, BEs showed a prevalence, increasing with time up to 78.3%. After therapy with TAM they persisted in 27.7% of cases. Two patients (3%) interrupted TAM therapy because of dizziness, and 3 patients (4%) interrupted bicalutamide therapy because of painful gynecomastia. In arm B, the prevalence of BEs was 35% after 12 months of therapy. The difference in BEs between the 2 arms was statistically significant (P < .0001). The differences in prevalence of gynecomastia and breast pain between the 2 arms both favored TAM prophylaxis (P < .0001 and P < .001, respectively). Up to 35% of patients had BEs of low intensity, never requiring bicalutamide withdrawal. Two patients (3%) interrupted the treatment because of gastrointestinal intolerance. No difference emerged between the 2 arms in terms of prostate-specific antigen (PSA) response, plasma testosterone levels, and tumor progression.

Conclusion: Bicalutamide-induced BEs can be prevented to a significant degree by prophylaxis with TAM 10 mg/day or effectively treated with TAM therapy 20 mg/day. Persisting BEs are of higher intensity after therapy than after prophylaxis.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anilides / adverse effects*
  • Anilides / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Chemotherapy, Adjuvant
  • Estrogen Antagonists / therapeutic use*
  • Gynecomastia / chemically induced
  • Gynecomastia / drug therapy*
  • Gynecomastia / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Nitriles / adverse effects*
  • Nitriles / therapeutic use
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / surgery
  • Statistics, Nonparametric
  • Tamoxifen / therapeutic use*
  • Tosyl Compounds / adverse effects*
  • Tosyl Compounds / therapeutic use
  • Treatment Outcome


  • Anilides
  • Antineoplastic Agents
  • Estrogen Antagonists
  • Nitriles
  • Tosyl Compounds
  • Tamoxifen
  • bicalutamide