Management Strategies for Hormone-Refractory Prostate Cancer

Abstract

There are a range of therapeutic options for the management of prostate cancer in patients in whom the disease has progressed despite hormone-deprivation therapy. These include second- and third-line hormone maneuvers, cytotoxic chemotherapy, systemic isotopes, bisphosphonates, biologically targeted agents, and palliative treatments such as external-beam radiotherapy. Optimal care requires clarity of purpose and experienced judgment of potential benefits and risks. The field has grown rapidly, and there is recent evidence of significant benefit from chemotherapy, in terms of both prolongation of life and symptom relief, using a regimen well tolerated in relatively elderly and infirm patients. The combination of docetaxel with prednisone has a clear role in patients with symptomatic hormone-refractory prostate cancer; however, a number of controversies exist, for example, the dose, cycle interval, duration of treatment, whether to combine docetaxel with other cytotoxic or biologically targeted agents, and its role in patients with asymptomatic disease. The overall benefit of bisphosphonate therapy is less clear in prostate cancer than in other malignancies. As our understanding of the biochemical basis of relative androgen-independence grows, development of targeted agents will become more appropriate and efficient. This is an active field of research and currently there are trials addressing both new cytotoxic agents, such as satraplatin and the epothilones, and a range of biological targets, including the vitamin D receptor, the endothelin A receptor, an augmented prostatic acid phosphatase antigen, as well as tumor angiogenesis.