Prolongation of off-cycle interval by finasteride is not associated with survival improvement in intermittent androgen deprivation therapy in LNCaP tumor model

Prostate. 2010 Feb 1;70(2):147-54. doi: 10.1002/pros.21046.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgen Antagonists
  • Androgens
  • Animals
  • Cell Cycle / drug effects*
  • Cell Line, Tumor*
  • Dihydrotestosterone / blood
  • Enzyme Inhibitors / pharmacology*
  • Estradiol / blood
  • Finasteride / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Orchiectomy*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics*
  • Survival Analysis
  • Testosterone / blood
  • Time Factors
  • Xenograft Model Antitumor Assays


  • Androgen Antagonists
  • Androgens
  • Enzyme Inhibitors
  • Dihydrotestosterone
  • Testosterone
  • Estradiol
  • Finasteride