A Study of Epirubicin With Estramustine Phosphate and Celecoxib for the Treatment of Prostate Cancer

• Epirubicin (Drug)
• Estramustine Phosphate (Drug)
• Celecoxib (Drug)

Primary outcomes

• Determine the effect of epirubicin with estramustine phosphate and celecoxib on PSA and objective response in patients with HRPC

Secondary outcomes

• Evaluate the toxicity of the combination of epirubicin with estramustine phosphate and celecoxib in patients with stage D3 prostate cancer.
• Determine the effects of this regimen on quality of life.
• Determine the survival of the patients treated with the proposed regimen.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Patient must have histologically proven adenocarcinoma of the prostate gland.
* Patient must have evidence of progressive metastatic disease (e.g., bone, pelvic mass, lymph node, liver or lung metastases) within 6 weeks prior to participation in the study.
* Patients must not have an elevated PSA level as the only evidence of disease. While castrated, the patients should have rising PSA on two consecutive measurements at least 1 week apart. The confirmatory PSA must be obtained within 1 week prior to study registration and should be >10ng/ml.
* Patients with bone metastases only (i.e., lacking soft-tissue disease) must have a PSA level of > 10 ng/ml. Patients with soft tissue metastases and /or visceral disease must have either measurable disease or a PSA level of > 10 ng/ml.
* Radiological evidence of hydronephrosis will not by itself constitute evidence of metastatic disease.
* Patients must have had prior treatment with bilateral orchiectomy or other primary hormonal therapy (e.g., estrogen therapy, LHRH analog + flutamide, etc.) with evidence of treatment failure.

NOTE: Patients who have not undergone bilateral orchiectomy must continue LHRH agonist therapy (e.g., depot leuprolide or goserelin) while receiving this protocol therapy.

* For patients previously treated with flutamide (Eulexin), nilutamide (Nilandron), or bicalutamide (Casodex): Patients must have discontinued flutamide or nilutamide < 4 weeks and for bicalutamide 6 weeks prior to registration.
* Patients should not have prior exposure to anthracyclines or estramustine phosphate.
* Patients must not have had prior radiotherapy < 4 weeks prior to this protocol treatment.
* Patients must not have previously received Strontium 89, Samarium 153, or other radioisotope therapies.
* Patients must have recovered from all toxicities due to prior treatment for prostate cancer prior to receiving this protocol treatment.
* Patients must have adequate bone marrow function: (WBC > 4000/ mm3, granulocytes > 2000/ mm3, platelet count > 100,000/mm3, and Hemoglobin > 8.0 g/dl < 4 weeks prior to participate in this study.
* Patients must have the following chemistry values < 4 weeks prior to participate in this study:
* Bilirubin < 1.5 mg/dl
* Transaminases (SGOT and/or SGPT) < 5 x institutional upper limit of normal (ULN)
* Creatinine < 2.0 mg/d. or creatinine clearance > 50 ml/min
* Alkaline phosphatase £ 5 x ULN
* Patients must have no active angina pectoris, or known heart disease of New York Heart Association Class III-IV. Patients must not have a history of myocardial infarction < 6 months prior to the study participation.
* Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been free of disease for the time period considered appropriate for the specific cancer.
* No serious concurrent medical illness or active infection should be present which would jeopardize the ability of the patient to receive the chemotherapy outlined in this protocol with reasonable safety.
* Sexually active patients must use an accepted and effective method of contraception while receiving protocol treatment.
* Patients must have a Karnofsky Performance Scale (KPS) score over 50. (Equaling ECOG Performance Scale of 0, 1, or 2).
* Age > 18 years.
* Patient must have failed the Taxotere treatment.

Exclusion Criteria:

• Results publication: Zhong F, Kasimis B, Hwang S, Cogswell J, Chang V, Morales E, Gonzalez M, Boholli I, Ohanian M, Blumenfrucht M: Second Line Treatment of Hormone Resistant Prostate Cancer (HRPC). A Phase II Trial of Epirubicin (E), Estramustine Phosphate (EP) and Celecoxib © Proc Am Soc Clin Oncol, Vol 24 #4754, 2005.

• Basil Kasimis, MD, Principal investigator, Department of Veterans Affairs NJ Health Care System