The Use of Transdermal Estrogen in Castrate-resistant, Steroid-refractory Prostate Cancer

Background: Androgen-deprivation therapy is the mainstay of treatment for metastatic prostate cancer. Corticosteroids and estrogens are also useful agents in castration-resistant prostate cancer (CRPC). However, oral estrogens are associated with thromboembolic events, which limits their use, and transdermal estrogens may offer a safer alternative. This study was carried out to determine the safety and effectiveness of transdermal estrogens in CRPC.

Patients and methods: Forty-one patients with CRPC and steroid-resistant prostate cancer were eligible for this dose-escalation study of transdermal estradiol. A starting dose of 50 mcg/24 hours was applied and increased if prostate-specific antigen (PSA) rose > 5 ng/mL in steps to 300 mcg/24 hours. The primary endpoint was PSA response, and secondary outcomes included incidence of thromboembolic events and progression-free survival. Patients who progressed were offered diethylstilbestrol.

Results: Five (13%) of 40 patients had > 50% PSA reduction for at least 1 month at any transdermal estradiol dose. No venous-thromboembolic events were observed, and responses plateaued at 200 mcg/24 hours. A correlation between PSA response and rising sex hormone binding globulin was seen. Fifty percent of patients subsequently responded to low-dose diethylstilbestrol.

Conclusion: Transdermal estradiol appears to be a low toxicity treatment option to control CRPC after failure of steroid therapy. Modulation of sex hormone binding globulin by transdermal estradiol may be one mechanism of action of estrogens on CRPC. Oral estrogens remain effective after the use of transdermal estradiol.