Treatment of Prostate Cancer by Induction of Alternate Cell Death Pathways: A Phase I Trial of Docetaxel, Estramustine, Mitoxantrone and Prednisone

Fecha de inicio: 1 de agosto de 1998

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Failure of complete androgen ablation (orchiectomy or LHRH and antiandrogen therapy) as manifested by at least 1 of the following criteria: Rise in serum PSA greater than 50% of nadir confirmed on 2 measurements 1 week apart Appearance of new lesions on bone scan Appearance of new soft-tissue lesions Measurable or evaluable disease No brain or leptomeningeal involvement PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Greater than 3 months Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) Alkaline phosphatase no greater than 5 times ULN SGOT and SGPT no greater than 2 times ULN Renal: Creatinine no greater than 2 times ULN Cardiovascular: No history of coagulopathy No myocardial infarction in the last 6 months No history of cardiovascular accident No history of congestive heart failure Neurological: No symptomatic peripheral neuropathy greater than grade 1 No history of significant neurologic or psychiatric disorders including psychotic disorders, dementia, or seizures Pulmonary: No history of pulmonary embolus Other: Testosterone no greater than 3.5 nmol/L No contraindications to glucocorticoid therapy such as uncontrolled diabetes mellitus or active peptic ulcer disease No active infection No other serious illness or medical condition No other concurrent or prior malignancy in the past 5 years except previously excised or curatively irradiated nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy Endocrine therapy: See Disease Characteristics At least 4 weeks since prior hormonal therapy (including nonsteroidal antiandrogens, but not LHRH agonists) Radiotherapy: No prior radiotherapy to greater than 30% of bone marrow At least 6 weeks since isotope therapy At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics Other: At least 4 weeks since prior investigational drugs