Treatment of hormone-refractory prostate cancer (HRPC) historically has shown limited efficacy. However, taxane-based chemotherapy regimens recently have demonstrated more promising results. Several groups have reported significant efficacy and minimal toxicity in patients with hormone-refractory disease receiving estramustine plus docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA). Others have demonstrated single-agent activity of platinum compounds in HRPC. Therefore, the combination of estramustine, docetaxel, and carboplatin is currently being tested in two separate trials of HRPC. The first is a Dana-Farber/Partners Cancer Care phase I study of estramustine, carboplatin, and escalating doses of weekly docetaxel. The second study is a Cancer and Leukemia Group B multicenter phase II study evaluating the combination of estramustine, docetaxel, carboplatin, and granulocyte colony-stimulating factor. The promise of taxane-based regimens in the treatment of hormone-refractory disease has led to consideration of treating patients at high risk for developing metastatic disease earlier in their clinical course. At Dana-Farber/ Partners Cancer Care, we are evaluating neoadjuvant weekly docetaxel alone followed by surgery in patients with high-risk localized prostate cancer using pathologic response as the primary end point. Adding carboplatin to the active combination of estramustine and docetaxel may improve the response rate in HRPC. Furthermore, the use of promising chemotherapy agents earlier in high-risk localized disease may improve clinical outcomes in these patients by decreasing their risk for systemic relapse.