Tumor regression and growth rates determined in two intramural NCI prostate cancer trials: The growth rate constant as an indicator of therapeutic efficacy.
133 Background: Like ATTP [bevacizumab + thalidomide + docetaxel + prednisone], ARTP [bevacizumab + lenalidomide + docetaxel + prednisone] is active in CRPC and in both the data suggest acquired resistance does not develop, supporting a strategy that continues therapy if tolerable. Discerning amongst new therapies in CRPC would be helped by novel assessment strategies that yield answers from smaller trials and allow comparisons across trials. We have validated a novel assessment method that quantifies tumor regression (d) and growth (g) rate constants using data obtained while pts are treated in a trial. We utilized this method to evaluate a phase II trial of ARTP in CRPC contrasting this with a previous study using thalidomide instead of lenalidomide (ATTP). Methods: Using PSA values and a two-phase mathematical equation we determined d and g. A three-phase equation was used to determine resistant fractions. Results: The median log g value with ARTP (-2.84) was statistically similar (p=0.204) to that observed with ATTP (-3.16). Both therapies had similar effects on log d (ARTP=-2.18; ATTP=-2.64; p=0.404). In a subset of pts with robust data both regimen are highly effective with only 3.01% and 5.46% of tumor resistant to ATTP and ARTP, respectively. In individual pt, statistically valid g and d values could be estimated after the fourth PSA value had been obtained, long before PSA increased - providing an early indicator of treatment failure. In most pts receiving prolonged treatment – as long as 700 d – the growth rate constant did not change, despite rising PSA values, indicating acquired resistance did not develop, and that if tolerable, therapy can be continued for longer periods of time. Conclusions: The substitution of daily thalidomide with lenalidomide 14/21 days in ARTP resulted in a combination statistically as effective as ATTP. As with ATTP majority of pts experienced marked reductions in the tumor’s g, and surprisingly in most, there was no evidence of acquired resistance, g remaining unchanged over prolonged time periods. Given the tolerability of this combination, pts with marked reductions in g may benefit from prolonged ARTP therapy.