The Treatment of Hormone Refractory Prostate Cancer

Abstract

Hormone refractory prostate cancer (HRPCA) is generally defined as: (1) consecutive PSA rise on three serial measures occuring a minimum of 1 week from the reference value, (2) testosterone serum levels equal to castrate levels (<50 ng/ml), (3) PSA rise following anti-androgen withdrawal or following the addition of secondary hormonal manipulations. HRPCA includes a heterogeneous group of patients with variable rates of tumour growth and it is evident that survival rates of these different groups will differ significantly and that these parameters have to be accounted for when designing and analyzing future trials in HRPCA. Currently, chemotherapy is not curative. However, with new developments chemotherapy can be effective in prolonging life and in providing definite palliation. For patients with advanced symptomatic HRPCA, mitoxantrone/prednisone, docetaxel or bisphosphonates (BP) result in significant improvements with regard to pain reduction and to the daily use of narcotics. Improvement in quality of life, pain reduction, and improvement in fatigue may be clinically appropriate endpoints for palliative clinical trials. For those patients with HRPCA characterized by rising PSA levels or by measurable asymptomatic disease, prospective randomized clinical phase III studies are needed to define the role of the different effective chemotherapeutic approaches which have been tested in phase II studies. Currently, taxanes as single agents or in combination with estramustine phosphate (EMP) appear to represent the most effective drugs although a prolongation of survival has not been demonstrated for any chemotherapeutic approach. In the future, monoclonal antibodies, signal transduction inhibitors targeting growth factors, neovascularisation and apoptosis will be evaluated in clinical phase II and III trials.