Oral cyclophosphamide and oral hydroxyurea in the treatment of hormone refractory prostate cancer in rats.

Hormone refractory prostate cancer is a fatal disease and currently no standard cytotoxic chemotherapy exists for prostate cancer. The recent use of prostate specific antigen as an endpoint for clinical trial has resulted in the ability to test the activity of chemotherapy agents in a quick manner. The aim of this study was to investigate the activity of the oral combination of two familiar agents, cyclophosphamide and hydroxyurea, against hormone refractory prostate cancer. In vitro studies demonstrated that hydroxyurea was more active than cyclophosphamide against the anaplastic Dunning rat prostate cancer cell line, Mat-LyLu. In vivo experiments, however, demonstrated cyclophosphamide to be superior to hydroxyurea. The combination of both agents failed to enhance inhibition of subcutaneously implanted Mat-LyLu cells. A human trial of oral cyclophosphamide using prostate specific antigen as an intermediate endpoint may be warranted.