OBJECTIVES:

Bicalutamide-induced gynecomastia is a side-effect that can severely limit quality of life and use of this agent. Several prophylactic strategies exist for this potential side-effect including hormone therapy and radiotherapy. We performed a network meta-analysis(NMA) to compare all regimens simultaneously, to determine which therapy has the best results.

METHODS:

A systematic review was performed through MEDLINE, Cochrane Central Register of Controlled Trials and meeting abstracts to identify RCTs testing treatments for Bicalutamide-induced gynecomastia. Treatments included radiotherapy(RT) and hormone therapy with either Anastrazole(ANZ) or Tamoxifen(TMX) compared to no treatment/placebo(NoTx). The primary endpoint was number of breast-events for gynecomastia development. Odds Ratio(OR) was the effect size of choice. A frequentist NMA was used to compare treatments; random–effects model was used. All test were 2-sided with an alpha = 0.05.

RESULTS:

6 studies involving 1066 patients were identified (Boccardo 2005, Fradet 2007, Perdona 2005, Saltzein 2005, Tyrell 2005, Widmark 2003), with 4 distinct treatments: RT (n=277), ANZ (n=90), TMX (n=280) and NoTx (n=419). Gynecomastia occurred in 84% (352/419) of patients with NoTx, 66% (59/90) with ANZ, 43% (119/277) with RT, and 18% (50/280) with TMX. TMX was significantly better than RT (OR 5.48 [1.68, 17.83]), ANZ (OR 7.19 [2.32, 22.24]) and NoTx (OR 25.40 [10.29, 62.72]). RT were significantly better than NoTx (OR 4.64 [1.88, 11.47]), but did not reach significance compared to ANZ (OR 1.31 [0.30, 5.74]). ANZ was significantly better than NoTx (OR 3.54[1.03,12.11]). RT and ANZ were significantly worse compared to TMX in terms of gynecomastia development.

CONCLUSIONS:

TMX was the best prophylactic treatment choice, significantly better than RT and ANZ, which were all significantly better than NoTx in terms of prevention of Bicalutamide-induced gynecomastia.