PURPOSE: Although estrogens have known antitumor activity in androgen independent prostate cancer, the best studied agent, diethylstilbestrol, is no longer commercially available in the United States. We tested 2 doses of the conjugated estrogen Premarin(R) in patients with androgen independent prostate cancer to determine the efficacy and safety of this widely available medication. MATERIALS AND METHODS: A total of 45 patients with progressive androgen independent prostate cancer were randomly assigned to receive Premarin 1.25 mg once (17) or 3 times (28) daily. Warfarin 1 mg daily was administered to all patients to minimize risk of thromboembolism. Low dose prophylactic breast irradiation was administered to most patients. RESULTS: Of the patients receiving high dosePremarin 25% achieved a 50% or greater reduction in prostate specific antigen. No patients treated with low dose Premarin reached a 50% reduction in prostate specific antigen. After 3 months of treatment, 11 patients (39.3%) on the high dose arm and 6 patients (35.3%) on the low dose arm showed no signs of progression. Three patients (6.7%) had a thromboembolic event. No significant gynecomastia was noted. A significant difference in dehydroepiandrosterone sulfate levels was detected between those who did and did not respond to Premarin (p = 0.03). CONCLUSIONS: High dose Premarin resulted in prostate specific antigen decreases of 50% or greater in 25% of patients with androgen independent prostate cancer. More than a third of patients receiving high or low dose Premarin maintained stable disease for at least 3 months. With concurrent warfarin 1 mg treatment, 6.7% experienced thromboembolic complications. Premarin 1.25 mg 3 times daily is a reasonable therapeutic option for patients with androgen independent disease.
RCT Entities:
PURPOSE: Although estrogens have known antitumor activity in androgen independent prostate cancer, the best studied agent, diethylstilbestrol, is no longer commercially available in the United States. We tested 2 doses of the conjugated estrogen Premarin(R) in patients with androgen independent prostate cancer to determine the efficacy and safety of this widely available medication. MATERIALS AND METHODS: A total of 45 patients with progressive androgen independent prostate cancer were randomly assigned to receive Premarin 1.25 mg once (17) or 3 times (28) daily. Warfarin 1 mg daily was administered to all patients to minimize risk of thromboembolism. Low dose prophylactic breast irradiation was administered to most patients. RESULTS: Of the patients receiving high dose Premarin 25% achieved a 50% or greater reduction in prostate specific antigen. No patients treated with low dose Premarin reached a 50% reduction in prostate specific antigen. After 3 months of treatment, 11 patients (39.3%) on the high dose arm and 6 patients (35.3%) on the low dose arm showed no signs of progression. Three patients (6.7%) had a thromboembolic event. No significant gynecomastia was noted. A significant difference in dehydroepiandrosterone sulfate levels was detected between those who did and did not respond to Premarin (p = 0.03). CONCLUSIONS: High dose Premarin resulted in prostate specific antigen decreases of 50% or greater in 25% of patients with androgen independent prostate cancer. More than a third of patients receiving high or low dose Premarin maintained stable disease for at least 3 months. With concurrent warfarin 1 mg treatment, 6.7% experienced thromboembolic complications. Premarin 1.25 mg 3 times daily is a reasonable therapeutic option for patients with androgen independent disease.
Authors: Jim C Hu; Stephen B Williams; A James O'Malley; Matthew R Smith; Paul L Nguyen; Nancy L Keating Journal: Eur Urol Date: 2012-02-01 Impact factor: 20.096
Authors: Bruce Montgomery; Peter S Nelson; Robert Vessella; Tom Kalhorn; David Hess; Eva Corey Journal: BMC Cancer Date: 2010-05-28 Impact factor: 4.430
Authors: Daniel Heudobler; Michael Rechenmacher; Florian Lüke; Martin Vogelhuber; Sebastian Klobuch; Simone Thomas; Tobias Pukrop; Christina Hackl; Wolfgang Herr; Lina Ghibelli; Christopher Gerner; Albrecht Reichle Journal: Front Pharmacol Date: 2018-11-28 Impact factor: 5.810