Background: We have previously reported that finasteride administration in intermittent androgen deprivation therapy (IADT) can improve survival of nude mice bearing LNCaP xenograft tumors when the duration of off-cycle in IADT was fixed. A recent retrospective study showed that addition of finasteride doubled the duration of the off-cycle, without changing progression to castration resistance. In view of the above difference, we attempted to investigate the relationship of 5alpha-reductase inhibition with the off-cycle interval and overall survival in a murine model.
Methods: Subcutaneous LNCaP tumors were established in nude mice (Balb/C-Nu). After the tumors reached a size of 0.5 cm in diameter, the mice were castrated and followed up for 2 weeks after which they were randomized to continuous androgen deprivation (CAD), CAD plus finasteride, IADT, and IADT plus finasteride. The off-cycle was discontinued when the tumor volume was doubled. Subsequent cycles were carried out similarly.
Results: Use of finasteride during the off-cycle of IADT doubled the first off-cycle duration. However, prolongation of the off-cycle by finasteride did not translate into an increase in overall survival.
Conclusions: The survival advantage of IADT + finasteride over IADT that we previously reported was lost when the off-cycle prolongation by finasteride was allowed. Maximum possible lengthening of the off-cycle by 5alpha-reductase inhibition is not associated with survival improvement in this animal model.