Post-therapy change in prostate-specific antigen levels as a clinical trial endpoint in hormone-refractory prostatic cancer : a trial with 10-ethyl-deaza-aminopterin

Serial changes in prostate-specific antigen (PSA) correlate with disease status in all stages of prostatic cancer. For hormone-refractory disease, post-therapy declines of 50% and 80% from baseline are associated with an improved survival. This study sought to evaluate edatrexate, a synthetic antifolate, in hormone-refractory prostatic cancer using post-therapy PSA change as the initial endpoint. Fourteen patients with progression of disease despite castrate levels of testosterone received edatrexate. Serial changes in PSA were monitored and correlated with other parameters of outcome. Stabilization of a rising PSA level in parallel with clinical stabilization of disease was observed in one patient; disease in all others progressed. Toxic reactions were acceptable. With no objective evidence for antitumor activity as assessed by post-therapy PSA changes in any of the patients treated, edatrexate seems a poor candidate for future study. The use of post-therapy PSA change as the initial screening modality allows treatments to be evaluated rapidly in patients without measurable disease. The methodology proposed will require validation in prospective phase III investigations using survival as the endpoint.