Phase II Trial of Transdermal Estradiol for Hormone Refractory Prostate Cancer

Inclusion Criteria * Patients with metastatic prostate adenocarcinoma, who have failed initial hormone therapy and who have had progression after at least one chemotherapy regimen that included docetaxel. Patients on antiandrogens must have progression after withdrawal of the antiandrogen for 4 weeks (flutamide) or 6 weeks (bicalutamide). * PSA ≥ 10 ng/ml. * Patients who have received LHRH agonist therapy for \> 1 month must maintain agonist therapy while on-study. Patients who have not received agonist therapy or received \< 1 month of therapy, may not begin or continue agonist therapy while on-study. * Age \>18 years and an estimated life expectancy of at least 4 months. * ECOG performance status ≤ 2 (see Appendix B). * Full recovery from the effects of any prior surgery or radiation therapy within 4 weeks of study entry. * Serum creatinine ≤ 1.5 x ULN * Total bilirubin \< ULN * Transaminases (SGOT and/or SGPT) ≤ 2 X institutional upper limit. * Capacity to give informed, written consent. Exclusion Criteria * Any coexisting medical condition precluding full compliance with the study. * Any history of deep venous thrombosis (DVT) or pulmonary embolus. Patients with a DVT on anticoagulants for ≥ 6 months will be eligible. * Known CNS metastasis. * The discontinuation of flutamide or bicalutamide \< 4 or 6 weeks respectively. * History of severe cardiovascular disease (AHA class III or IV; see Appendix C), uncontrolled CHF or life threatening cardiac dysrhythmia in the past 6 months. * Herbal supplements may not be used while on-study and patients must have discontinued use for ≥ 1 week before entering on-study. * Patients with a known hypersensitivity to estrogen. * Triglyceride \> 200 mg/dl. * Prior estramustine.