APPLES AND ORANGES - BUILDING A CONSENSUS FOR STANDARDIZED ELIGIBILITY CRITERIA AND END-POINTS IN PROSTATE-CANCER CLINICAL-TRIALS

Purpose: To survey eligibility and response criteria for clinical tria ls in hormone refractory prostate cancer (HRPC). Methods: Thirty-five established investigators of HRPC completed a 125-question survey Resu lts: There was a general consensus that criteria total trial entry wou ld include progression based on an increasing prostate-specific antige n (PSA) level (94% of investigators), an increase in measurable diseas e (91%), and/or appearance of new bone lesions on bone scan (83%), Mos t believed that castrate levels of testosterone (77%) and progression after antiandrogen withdrawal (97%) should be documented before study enrollment. Continuation of testicular androgen suppression would be r equired by 82%, Seventy-seven percent favored separate reports on resp onse rates in bone, measurable disease, symptoms, and biochemical mark ers (primarily PSA levels), rather than a composite response, Ninety-f our percent of the investigators accepted changes in PSA level as a su rrogate end point of response. However, interpretation by these invest igators tors of a PSA data set similar to what might be observed in a clinical trial showed marked discordance, Survival is the end point of most importance to 94% of these investigators. Response based on chan ges in measurable disease, time to progression, response duration, PSA level decrease, or quality of life improvement were of similar weight ed value as a clinical trial end point and were rated as less importan t to these investigators than survival (P < 10(-8)). Conclusion: This survey indicates some consensus on eligibility and concomitant treatme nts for clinical studies in HRPC, The use of multiparameter assessment of response and PSA level as a surrogate end point have been widely a dopted.