Management of bicalutamide induced gynaecomastia. A randomized study comparing therapy versus prophylaxis with tamoxifen.

Introduction and Objective: Gynaecomastia is a potentially treatment limiting adverse event of antiandrogen monotherapy for prostate cancer. Tamoxifen has shown to be effective in therapy and prophylaxis of gynecomastia and breast pain. However, tamoxifene dosage and treatment duration are not established and debate still exists if prophylaxis is more effective than therapy at the early onset. This randomized study compared the prophylactic activity of tamoxifene at the dose of 10 mg with its therapeutic activity when given at the dose of 20 mg at the early appearance of gynecomastia in patients receiving bicalutamide 150 mg/d for prostate cancer. Methods: Between June 2005 and June 2007, 176 patients (median age 74 years), affected by prostate cancer have been randomized, at the moment of bicalutamide prescription, in to 2 arms according to gynecomastia treatment with tamoxifen. Arm A: Tamoxifen 20 mg/daily given for one year starting at the early onset of gynecomastia (within one month); tamoxifen 10 mg/daily given for one year starting at the prescription of bicalutamide. Routine laboratory exams, testosterone, PSA and follow-up visits were obtained at one month and then 3-monthly. Gynecomastia and breast pain were evaluated by the patients through a self-administered visual analog scale. Moreover, gynecomastia was classified into 4 grades (0-4) by physical examination. Results: At a follow-up between 3 and 24 months, gynecomastia increased in arm A from 34% at 3 months up to 78% after 12 months of bicalutamide therapy. When tamoxifen 20mg was given all patients showed gynecomastia and breast pain reduction, not vanishing, however, in 56% and 34% of cases respectively. Two patients interrupted the treatment after 3 months due to dizziness and 4 (5%) patients did not considered relevant the gynecomastia and did not take the drug. The incidence of gynecomastia and breast pain was significantly reduced (p<0.0001) by tamoxifen 10 mg prophylaxis but not completely abolished. Both gynecomastia and breast pain increased up to 25% after one year of bicalutamide plus tamoxifene administration. No patient interrupted the treatment due to intolerance. No significant difference emerged between the 2 groups in term of PSA response and plasma testosterone levels. Conclusions: Bicalutamide induced gynaecomastia is significantly reduced but not abolished by tamoxifen 10 mg prophylaxis. Gynecomastia and breast pain, although reduced, persists after tamoxifen 20 mg given at the early onset in 56% and 34% of the patients respectively.