Treatment options in androgen-independent prostate cancer.

Metastatic prostate cancer is a leading cause of cancer-related death in men. Although most patients will respond to androgen ablation as initial systemic therapy, nearly all patients will develop androgen-independent prostate cancer (AI CaP) and will succumb to the disease. Advances in molecular biology have demonstrated mutations in and persistent expression of the human androgen receptor in metastatic disease. Furthermore, recent evidence indicates that an apoptotic block through p53 mutations or bcl-2 overexpression may have a potential role in the poor responses seen with standard chemotherapy. Presently, the six general treatment options available for AI CaP are best supportive care, radiation therapy, radioisotopes, secondline hormonal therapy, chemotherapy (single agent or combination), and investigational therapies such as monoclonal antibodies, cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors, and antiangiogenesis agents, among others. None of these modalities have produced durable remissions, although some have demonstrated palliative benefit. The next generation of clinical trials should not consist of futile hormonal manipulations or repetitive chemotherapy. Therapeutic strategies aimed at circumventing molecular blocks to cell death or targeting unique cancer molecules and genes will be more likely to improve quality of life and longevity. Furthermore, the aggressive use of palliative care will ensure effective caring for patients and the healing of families in the absence of cure.