title: Prolongation of off-cycle interval by finasteride is not associated with survival improvement in intermittent androgen deprivation therapy in LNCaP tumor model.
abstract: 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.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Shubham
authors.initials: S
authors.lastname: Gupta
authors.forename: Vi
authors.initials: V
authors.lastname: Hua
authors.forename: Raquel
authors.initials: R
authors.lastname: Ramos-Garcia
authors.forename: Daniel
authors.initials: D
authors.lastname: Shevrin
authors.forename: Borko D
authors.initials: BD
authors.lastname: Jovanovic
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: 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
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D018120:Finasteride