Phase II Trial of Transdermal Estradiol for Hormone Refractory Prostate Cancer

• To evaluate the toxicities of the use of transdermal estradiol in patients with HRPC after initial chemotherapy. To measure quality of life of patients receiving therapy with the Functional Assessment of Cancer Therapy-Prostate scale (FACT-P). [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• To evaluate measurable disease response in patients with hormone and chemotherapy refractory prostate cancer. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• To evaluate time to progression. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
• To assess the plateau level of estradiol that is attained with the dose of 0.4mg/day given via transdermal estradiol patch and in addition, assess the response on testosterone in the androgen resistant population. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

• • To evaluate the toxicities of the use of transdermal estradiol in patients with HRPC after initial chemotherapy.
• • To measure quality of life of patients receiving therapy with the Functional Assessment of Cancer Therapy-Prostate scale (FACT-P).
• • To evaluate measurable disease response in patients with hormone and chemotherapy refractory prostate cancer.
• • To evaluate time to progression.
• • To assess the plateau level of estradiol that is attained with the dose of 0.4mg/day given via transdermal estradiol patch and in addition, assess the response on testosterone in the androgen resistant population.

Multiple trials have shown the efficacy of estrogen therapy in metastatic prostate cancer, and most recently trials have supported the use of transdermal estrogens (patch) in the patient population with a decreased risk of cardiovascular disease as compared to the oral estrogens. We plan to study(estrogen patch) at a dose of 0.4mg qd. We will evaluate the toxicities and measure quality of life. We will assess PSA response and measurable disease response. This will be a trial available to the Cancer Institute of New Jersey Oncology Group. We will enroll a total of 33 patients. We will plan to enroll 10 at CINJ.Patients will wear the patches (4) continuously. We will obtain blood work and clinic evaluations every three weeks. We will assess quality of life through a questionnaire given to patient every three weeks.

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.