RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells.
Anticoagulant drugs such as warfarin may reduce the risk of blood clots.
PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus warfarin
in treating patients who have prostate cancer.
OBJECTIVES: I. Determine the safety, efficacy, and durability of docetaxel and estramustine
followed by doxorubicin and ketoconazole in patients with high-risk, androgen-independent
prostate cancer. II. Determine whether anticoagulation with warfarin can reduce the
frequency of thromboembolic complications associated with estramustine in these patients.
OUTLINE: Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and
docetaxel IV over 1 hour on day 3 weekly. Patients also receive oral warfarin daily.
Treatment repeats every 4 weeks for a total of 2 courses in the absence of disease
progression or unacceptable toxicity. Regimen B: After completion of regimen A, patients
receive doxorubicin IV over 30 minutes weekly and oral ketoconazole twice daily. Treatment
repeats every 4 weeks for a total of 2 courses in the absence of disease progression or
unacceptable toxicity. Patients are followed monthly until disease progression.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 1 year.
DISEASE CHARACTERISTICS: Histologically confirmed prostate cancer High risk as defined by
any 2 of the following: Karnofsky performance status of 70-80% Lactate dehydrogenase
greater than 200 U/mL Hemoglobin less than 13 g/dL Prostate-specific antigen (PSA) at
least 4 ng/mL Progressive disease based on any 1 of the following: Rise in PSA level of at
least 25% above baseline At least 3 determinations taken at weekly intervals OR At least 2
determinations taken at monthly intervals New or progressive soft tissue masses on MRI or
CT scan Radionucleotide bone scan with new metastatic lesion(s) Serum testosterone no
greater than 30 ng/mL If no prior surgical orchiectomy, castrate levels of serum
testosterone must be maintained with continuation of gonadotropin releasing hormone
analogs If receiving an anti-androgen, must show progression of disease after stopping
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: See Disease Characteristics
Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: See Disease
Characteristics WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic:
Bilirubin normal SGOT/SGPT no greater than 1.5 times upper limit of normal (ULN) Renal:
Creatinine no greater than 1.5 times ULN Cardiovascular: No significant cardiovascular
disease No New York Heart Association class III or IV heart disease No active angina
pectoris No myocardial infarction within the last 6 months Ejection fraction at least 45%
by echocardiogram or MUGA No prior hemorrhagic or thrombotic cerebral vascular accident No
deep venous thrombosis Pulmonary: No pulmonary embolism within the past 6 months Other: No
history of bleeding disorder or gastrointestinal bleeding that would preclude
anticoagulation with warfarin No other concurrent malignancy except non-melanoma skin
cancer or any curatively treated malignancy considered to be at less than 30% risk of
relapse No severe infection No severe malnutrition No other serious medical illness that
would preclude study
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No more than 1
prior chemotherapy regimen Endocrine therapy: See Disease Characteristics Radiotherapy: No
more than 1 prior course of palliative radiotherapy No more than 1 prior radioisotope
therapy with strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium Surgery:
See Disease Characteristics At least 4 weeks since prior major surgery