A retrospective analysis of intramural NCI prostate cancer trials: Progress made and insights gleaned.

Abstract

4657 Background: In solid tumors such as prostate cancer, novel paradigms are needed to assess therapeutic efficacy. We describe a method for estimating PSA growth and regression rate constants from serial PSA measurements. We assessed the method's potential in patients with metastatic castration resistant prostate cancer (CRPC). Methods: Patients with CRPC enrolled in five phase II studies conducted over more than a decade were evaluated. The studies represent the evolution of CRPC therapy, and include a vaccine trial. PSA measurements obtained prior to, and during, therapy were used. Data analysis using a two-phase mathematical equation yielded concomitant PSA growth and regression rate constants Results: Incremental reductions in growth rate constants were recorded in successive chemotherapy trials enrolling similar patients. Growth rate constants correlated with survival, except in patients receiving a vaccine-based therapy where the evidence demonstrates prolonged survival presumably due to immunity developing subsequent to vaccine administration. In combination chemotherapy trials the analysis suggests prolonging drug exposure could have increased survival Conclusions: Incremental reductions in tumor growth rate constants suggest increased efficacy in successive trials. Because the derived growth rate constant correlates with survival, it may be useful in clinical trials to assess differences in efficacy. The PSA-TRICOM vaccine appears to have provided marked benefit not apparent during vaccination, but consistent with development of a growth-retarding immune response. If validated as a surrogate for survival the growth rate constant would offer an important new efficacy endpoint for clinical trials. Finally, pursuit of what appear to be very promising results with a PSA-TRICOM vaccine is warranted. No significant financial relationships to disclose.