Therapy for hormone-resistant prostate cancer: no longer a myth

Androgen ablation, initially effective in 80% of patients with advanced prostate cancer, does not cure. In 1996, it is estimated that 41,500 men will die from hormone-resistant metastatic prostate cancer, ranking it the second leading cause of cancer death in the United States [1]. Past options for patients who fail androgen ablation were limited, with most cytotoxic agents being ineffective or having minimal antitumor activity. Two reviews of chemotherapy for hormone-refractory prostate cancer found response rates of 6.5% (95% [confidence intervals] (CI), 5.6%–7.4%) [2] and 8.7% (95%CI, 6,4%–9.0%) [3], respectively, in 1683 and 1001 adequately treated patients. Despite such dismal results, progress in treatment of hormone-refractory prostate cancer has occured in the three years since the last review. The use of human prostate cancer cells in vitro and in vivo animal models to evaluate drug synergy has identified promising new drugs and combinations for evaluation in phase II trials. Durable responses, in some cases lasting more than one year, have been observed in patients treated with these therapies. Significant progress has also been achieved in the management of cancer pain. Along with these treatment advances, important observations have been made regarding the clinical behavior of metastatic prostate cancer, which have had direct implications not only for identifying active drugs, but also for trial methodology. The use of tumor markers to measure response, as well as the recognition of potentially confounding factors (e.g., flutamide withdrawal and the use of corticosteroids) have allowed for more rapid and precise evaluation of these drugs and have also helped to set the standard for future trials. This article reviews some of the more promising developments in the evaluation and treatment of hormone-resistant prostate cancer.