Paclitaxel, Topotecan, and Estramustine in Treating Patients With Metastatic Hormone-Refractory Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as paclitaxel, topotecan, and estramustine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one chemotherapy drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving paclitaxel, topotecan, and estramustine together works in treating patients with metastatic hormone therapy-refractory prostate cancer.

Detailed Description
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OBJECTIVES: Primary Determine the objective response rate in patients with metastatic hormone-refractory prostate cancer treated with paclitaxel, topotecan, and estramustine. Determine the progression-free and overall survival of patients treated with this regimen. Determine the toxic effects of this regimen in these patients. Determine the pharmacokinetics of this regimen in these patients. Secondary Determine the frequency and number of circulating tumor cells in patients before and after treatment with this regimen and at disease progression. Determine the microtubule morphology, β-tubulin isotype pattern, apoptotic markers, and metaphase chromosome alignment in circulating tumor cells in patients before and after treatment with this regimen and at disease progression. OUTLINE: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15; topotecan IV over 30 minutes on days 2, 9, and 16; and oral estramustine twice daily on days 1 and 2 of course 1 and on days 0-2, 7-9, and 14-16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 18-38 patients will be accrued for this study.

Official Title
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Phase II Study of the Activity of Weekly Paclitaxel, Topotecan Plus Oral Estramustine Phosphate in Metastatic Hormone-Refractory Prostate Carcinoma

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: estramustine phosphate sodium
* Drug: paclitaxel
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate gland Progressive metastatic disease (e.g., bone, pelvic mass, lymph node, liver or lung metastases) Radiologic evidence of hydronephrosis alone dose not constitute metastatic disease Failed prior primary hormonal therapy (e.g., estrogen therapy, luteinizing hormone-releasing hormone blocker and flutamide) or bilateral orchiectomy Patients previously treated with flutamide or bicalutamide must have evidence of disease progression i.e., increasing Prostate-Specific Antigen (PSA) PSA level ≥ 10 ng/mL if bone metastases only are present (i.e., lacking measurable soft tissue disease) No elevated serum acid phosphatase or PSA level as the only evidence of disease No carcinomatous meningitis or brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Eastern Cooperative Oncology Group (ECOG) 0-2 Life expectancy At least 12 weeks Hematopoietic White Blood Cell (WBC) ≥ 4,000/mm^3 OR Granulocyte count ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Serum Glutamic-Oxaloacetic Transaminase(SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) ≤ 2 times normal Bilirubin ≤ 1.5 mg/dL Renal Creatinine ≤ 2.0 mg/dL OR Creatinine clearance ≥ 50 mL/min Cardiovascular History of deep venous thrombosis allowed provided patients are maintained on therapeutic anticoagulation therapy No active angina pectoris No New York Heart Association class II-IV heart disease No myocardial infarction within the past 6 months No thrombosis within the past 3 months Other Fertile patients must use effective contraception during and for 3 months after study participation No active infection No other concurrent serious medical illness that would preclude study participation No other malignancy within the past 3 years except curatively treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy Endocrine therapy See Disease Characteristics At least 4 weeks since prior flutamide At least 8 weeks since prior bicalutamide Radiotherapy More than 4 weeks since prior radiotherapy No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium Surgery See Disease Characteristics Other Recovered from all prior therapy No prior cytotoxic therapy for prostate cancer No concurrent milk, milk products, antacids, calcium-containing drugs, or food during estramustine administration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: estramustine phosphate sodium|nan|
|Drug: paclitaxel|nan|
|Drug: topotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV prostate cancer, adenocarcinoma of the prostate