ORLANDO, FL (UroToday.com) - Intermittent Androgen Ablation (IAA) is under investigation as a means of improving quality of life and retarding progression to androgen independence. The decisions to terminate and reinstitute androgen withdrawal ("On" and "Off" cycle durations) are based on the serum PSA levels. This group of researchers has previously shown that adding finasteride (F) during the off cycle if IAA can improve survival in vivo by using fixed durations of off cycle treatments (Eggener etal, 2006). A recent retrospective study showed that addition of F doubled the duration of the off cycle, without changing progression to androgen independence (Scholz et al, 2006). In view of the above, these researchers attempted to determine the extent to which off cycle 5α-reductase inhibition could prolong the off cycle, and the effect such prolongation would have on overall survival in a murine model.

Subcutaneous LNCaP tumors were established in nude mice. After the tumors reached a size of 0.5cm, the mice were castrated and followed up for 2 weeks after which they were randomized to receive either Testosterone (T) (IAA group) or T+F (IAA + F group). Or nothing (continuous androgen ablation [CAA] group). The off cycle was discontinued when the tumor sizes increased by 40%. Subsequent cycles were carried out similarly. Testes-intact animals were kept as controls. PSA, T, and Dihydrotestosterone levels were assayed.

They report that off cycle F doubled the first off cycle duration. This increase in the duration of the off cycle did not translate into an increase in overall survival; rather the survival advantage of IAA+F over IAA that was previously reported was eliminated.

They conclude that off cycle F improves survival when the off cycles are similar relative to standard IAA. When the off cycle is allowed to increase maximally, the survival advantage is lost. Taken together, these results argue that maximum possible lengthening of the off cycle may diminish survival and may not be advisable. Further studies should focus on delineating the nature and the time-course of the pathways that improve survival in the IAA+F group, so as to best define the duration of the off cycle.

Presented by Yujuan Wang, Shubham Gupta, Daniel Shevrin, Joel B Nelson, Zhou Wang at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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