Non-hormone chemotherapy for prostate cancer: principles of treatment and application to the testing of new drugs.

Prostate cancer, one of the commonest malignancies in western society, remains a major challenge in management. Although the typical patient is elderly and may not withstand aggressive approaches to treatment, increasing numbers of our population survive to old age, while remaining healthy and active. As prostate cancer is a disease of old age, it is therefore likely that there will be an increased requirement to combat this disease in a fit patient population. Although hormonal manipulation provides effective first-line treatment for 70%-80% of patients with metastatic disease, the majority of these ultimately relapse. Cytotoxic chemotherapy has not provided a panacea for relapsed, hormone-resistant prostate cancer. Despite the significant subjective and objective responses that can be achieved by the use of single agents, the median survival of patients with hormone-resistant disease remains less than 12 months. The use of combination cytotoxic regimens has not altered this. New approaches, perhaps including the development of new cytotoxic agents, innovative uses of established drugs, or the application of the biological response modifiers will be required before this problem is resolved. Until then, we must not be satisfied with inadequate indices of success. The reporting of response rates and of survival statistics drawn from the small group of responding patients is no true indicator of success. Until truly effective treatment is available, we must learn to define more useful indicators of patient benefit, to be more effective in palliating the symptoms of this disease, and to be more critical of the limitations of our progress.