Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.
OBJECTIVE
To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning.


METHODS
A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed.


RESULTS
Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels.


CONCLUSIONS
Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.
Boccardo
F
F
University and National Cancer Research Institute, University of Genoa, Genoa, Italy. f.boccardo@unige.it
Rubagotti
A
A
Battaglia
M
M
Di Tonno
P
P
Selvaggi
F P
FP
Conti
G
G
Comeri
G
G
Bertaccini
A
A
Martorana
G
G
Galassi
P
P
Zattoni
F
F
Macchiarella
A
A
Siragusa
A
A
Muscas
G
G
Durand
F
F
Potenzoni
D
D
Manganelli
A
A
Ferraris
V
V
Montefiore
F
F
D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000813:Anilides / Q000009:adverse effects*; D001941:Breast Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D006177:Gynecomastia / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000517:prevention & control*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D011788:Quality of Life; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D013739:Testosterone; C053541:bicalutamide; D017430:Prostate-Specific Antigen