title: 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.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  Daily bicalutamide (150 mg) plus daily tamoxifen 20mg continuously (daily group) or the same but with tamoxifen at 20mg 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.
  
  
  METHODS
  For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires.
  
  
  CONCLUSIONS
  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 20mg/wk is inferior to tamoxifen 20mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20mg for the prophylaxis of bicalutamide-induced breast events were confirmed.
authors.affiliation: University of Genoa, Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rubagotti
authors.forename: Giario
authors.initials: G
authors.lastname: Conti
authors.forename: Francesco
authors.initials: F
authors.lastname: Francesca
authors.forename: Ottavio
authors.initials: O
authors.lastname: De Cobelli
authors.forename: Luca
authors.initials: L
authors.lastname: Canclini
authors.forename: Michele
authors.initials: M
authors.lastname: Gallucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Aragona
authors.forename: Pasquale
authors.initials: P
authors.lastname: Di Tonno
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortellini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Martorana
authors.forename: Alberto
authors.initials: A
authors.lastname: Lapini
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
mesh_terms: D000368:Aged; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D006177:Gynecomastia / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D013629:Tamoxifen / Q000008:administration & dosage*; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D009570:Nitriles; D014105:Tosyl Compounds; D013629:Tamoxifen; C053541:bicalutamide