POST-THERAPY CHANGE IN PROSTATE-SPECIFIC ANTIGEN LEVELS AS A CLINICAL-TRIAL END-POINT IN HORMONE-REFRACTORY PROSTATIC-CANCER - A TRIAL WITH10-ETHYL-DEAZA-AMINOPTERIN

Objectives. Serial changes in prostate-specific antigen (PSA) correlat e with disease status in all stages of prostatic cancer. For hormone-r efractory disease, post-therapy declines of 50% and 80% from baseline are associated with an improved survival. This study sought to evaluat e edatrexate, a synthetic antifolate, in hormone-refractory prostatic cancer using post-therapy PSA change as the initial endpoint. Methods. Fourteen patients with progression of disease despite castrate levels of testosterone received edatrexate. Serial changes in PSA were monit ored and correlated with other parameters of outcome. Results. Stabili zation of a rising PSA level in parallel with clinical stabilization o f disease was observed in one patient; disease in all others progresse d. Toxic reactions were acceptable. Conclusions. With no objective evi dence for antitumor activity as assessed by post-therapy PSA changes i n any of the patients treated, edatrexate seems a poor candidate for f uture study. The use of post-therapy PSA change as the initial screeni ng modality allows treatments to be evaluated rapidly in patients with out measurable disease. The methodology proposed will require validati on in prospective phase III investigations using survival as the endpo int.