Prolongation of off-cycle interval by finasteride is not associated with survival improvement in intermittent androgen deprivation therapy in LNCaP tumor model.
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.
Wang
Yujuan
Y
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Gupta
Shubham
S
Hua
Vi
V
Ramos-Garcia
Raquel
R
Shevrin
Daniel
D
Jovanovic
Borko D
BD
Nelson
Joel B
JB
Wang
Zhou
Z
D000726:Androgen Antagonists; D000728:Androgens; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D013196:Dihydrotestosterone / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D018120:Finasteride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000235:genetics*; D016019:Survival Analysis; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
D000726:Androgen Antagonists; D000728:Androgens; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D018120:Finasteride