Phase II study of low dose and high dose conjugated estrogen for androgen independent prostate cancer.
OBJECTIVE
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.


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.
Pomerantz
Mark
M
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Manola
Judith
J
Taplin
Mary-Ellen
ME
Bubley
Glenn
G
Inman
Margaret
M
Lowell
Jennifer
J
Beard
Clair
C
Kantoff
Philip W
PW
Oh
William K
WK
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D013739:Testosterone; D017430:Prostate-Specific Antigen