Treatment of hormone-refractory prostate cancer

Objective. An increasing number of patients with prostate cancer develop hormone-refractory disease after standard treatment modalities. In these patients, early clinical trials with chemotherapy produced disappointing response rates. However, clinical trials that employ response criteria such as prostate-specific antigen (PSA) and clinical benefit response have produced encouraging responses. This article reviews current and future treatment options for the management of hormone-refractory prostate cancer. Data Sources. A MEDLINE search for the years 1978 to 1998 was completed. The following terms were used in our search: prostate cancer, hormone-refractory, treatment, and chemotherapy. Relevant articles referenced in the literature obtained in our MEDLINE search were reviewed. Study Selection. Randomized and nonrandomized clinical trials were used in our review. Clinical trials using prostate-specific antigen or a palliation of symptoms as primary criteria for response were given priority. Data Synthesis. Several genetic alterations, including the overexpression of bcl-2 or mutations in p53, may lead to the development of hormone-refractory prostate cancer. Agents such as estramustine and taxanes, which affect microtubule function and potentially modulate bcl-2, appear to be particularly active in the treatment of hormone-refractory prostate cancer. In addition, mitoxantrone as well as other agents has been shown to be beneficial in improving the quality of life in patients with hormone-refractory prostate cancer. Conclusion. Hormone-refractory prostate cancer is not a chemotherapy-resistant disease as once believed; significant progress in the treatment of hormone-refractory prostate cancer has been made with new combinations of chemotherapy agents. Promising new treatments are currently under evaluation to assess their potential benefit over the standard treatment modalities that are currently available.