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

Inclusion Criteria

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