Treatment options in hormone-refractory prostate cancer: current and future approaches

Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone refractory prostate cancer (HRPC) have a median survival of approximately 18 months and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone. Until recently, cytotoxic chemotherapy was felt to be relatively ineffective in the treatment of HRPC. Combination regimens incorporating new active agents have demonstrated significant activity in this setting, renewing interest in the use of chemotherapy to treat HRPC. Recent advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumour cell. Biologic agents now in development include those capable of altering signal transduction, blocking angiogenesis, inhibiting cell cycle progression, and stimulating apoptosis. In addition, many types of immune therapies are showing promise. Evaluating these agents, and incorporating them into existing regimens, are major goals of ongoing clinical research in advanced prostate cancer.