title: Phase II study of low dose and high dose conjugated estrogen for androgen independent prostate cancer.
abstract: 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.
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Pomerantz
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.forename: Glenn
authors.initials: G
authors.lastname: Bubley
authors.forename: Margaret
authors.initials: M
authors.lastname: Inman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lowell
authors.forename: Clair
authors.initials: C
authors.lastname: Beard
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
mesh_terms: 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
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D013739:Testosterone; D017430:Prostate-Specific Antigen