The purpose of this study is to see if Premarin is useful against androgen-independent prostate cancer and to help understand how drugs such as Premarin may work.

Patients will be randomly assigned to one of two study groups (arm A or Arm B). Arm A will receive 1.25mg of Premarin once daily and arm B will receive 1.25mg of Premarin three times a day. Patients will also receive coumadin daily to help prevent thromboembolic disease.

After reviewing the first 30 patients on Arm A, it was determined that arm A (low dose Premarin) was not effective. Arm A was then closed and patients on Arm A were given the choice to switch to Arm B.

Treatment will continue until there is evidence of disease progression or unacceptable side effects.

Every 4 weeks while receiving Premarin, a physical exam and blood work will be performed. Every 12 weeks a CT scan of the abdomen and pelvis and a bone scan will be performed.

Patients will also be encouraged to undergo standard preventative breast irradiation prior to starting Premarin or up to 4 weeks after starting treatment.

Inclusion Criteria:

• Documented histologic evidence of prostate cancer.
• Progressive androgen-independent prostate cancer as defined by the Prostate-Specific Antigen (PSA) Working Group after conventional androgen deprivation and antiandrogen withdrawal.
• PSA > 2ng/ml and serum testosterone of < 50ng/ml
• No history of thromboembolic disease within the prior year
• ECOG performance status of 0-2
• Creatinine < 2 x upper limit of normal
• Bilirubin < 2 x upper limit of normal
• AST < 2 x upper limit of normal

Exclusion Criteria:

• Unstable angina or change in anginal symptoms within the past 6 months.
• Prior therapy with estrogens or PC-SPECS.
• Concurrent megestrol acetate or steroid hormones
• Major surgery or radiation therapy within 4 weeks
• Strontium-89 or samarium-153 therapy within 8 weeks