estramustine, docetaxel, and carboplatin in treating patients with prostate cancer that has not responded to hormone therapy

Conditions: Prostate Cancer

Summary: 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. purpose: phase i trial to study the effectiveness of estramustine, docetaxel, and carboplatin in treating patients who have prostate cancer that has not responded to hormonal therapy.

objectives: * determine the maximum tolerated dose of weekly docetaxel when combined with carboplatin and estramustine in patients with hormone refractory prostate cancer. * determine the safety and efficacy of this regimen in this patient population. outline: this is a dose escalation study of docetaxel. patients receive oral estramustine 3 times daily on days 1-5 and docetaxel iv over 1 hour on day 2 of weeks 1-3. patients also receive carboplatin iv over 1 hour on day 2 of week 1 only. treatment continues every 28 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. cohorts of 3-5 patients receive escalating doses of docetaxel until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 5 patients experience dose-limiting toxicity. projected accrual: a total of 20-30 patients will be accrued for this study within 12 months.

Eligibility criteria:
disease characteristics: * histologically confirmed adenocarcinoma of the prostate * disease progression following androgen ablation therapy (hormonal or surgical) by either: * increase in the product of bidimensional diameters of 1 or more radiographically documented sites of measurable disease or * two consecutive increases in psa documented over a previous reference value * first increase in psa should occur a minimum of 1 week from the reference value and be confirmed * first psa value is less than the previous value, then patient is eligible provided next psa is greater than the second psa * testosterone levels documented in the castrate range (i.e., less than 30 ng/ml) patient characteristics: age: * 18 to 85 performance status: * calgb 0-2 life expectancy: * not specified hematopoietic: * wbc at least 3,000/mm3 * platelet count at least 100,000/mm3 hepatic: * bilirubin normal * sgot no greater than 2.5 times upper limit of normal (uln) if alkaline phosphatase normal or * alkaline phosphatase no greater than 4 times uln if sgot normal or * sgot no greater than 1.5 times uln and alkaline phosphatase no greater than 2.5 times uln renal: * creatinine no greater than 2.0 mg/dl cardiovascular: * no myocardial infarction within past year * no significant change in anginal pattern within past 6 months * no new york heart association class ii-iv heart disease * no deep venous thrombosis within past year other: * no significant peripheral neuropathy prior concurrent therapy: biologic therapy: * not specified chemotherapy: * prior chemotherapy allowed except taxanes or platinum derivatives endocrine therapy: * see disease characteristics * at least 4 weeks since prior antiandrogens radiotherapy: * at least 4 weeks since prior radiotherapy surgery: * see disease characteristics

Keywords: adenocarcinoma of the prostate recurrent prostate cancer