The preventive and therapeutic efficacy of finasteride and dutasteride in TRAMP mice

The Prostate Cancer Prevention Trial and Reduction by Dutasteride of Prostate Cancer Events trial found that the 5α‐reductase (5αR) inhibitors finasteride and dutasteride, respectively, decreased prostate cancer prevalence but also increased the incidence of high‐grade tumors. Because finasteride only inhibits 5αR2, we hypothesized that finasteride would not be as efficacious in preventing prostate cancer development in C57xFVB TRAMP mice as dutasteride, which inhibits both 5αR1 and 5αR2. Six week old mice were randomized to a control AIN93G or pre‐and post‐finasteride and dutasteride diet (83.3 mg drug/kg diet) groups (n =30–33) that began at 6 and 12 weeks of age, respectively, and terminated at 20 weeks of age. The pre‐and post‐groups were designed to test the preventive and therapeutic efficacy of the drugs, respectively. Final body weights were decreased in the pre‐dutasteride group and genitourinary tract weights were decreased in pre‐finasteride, pre‐and post‐dutasteride groups. The incidence of low‐grade and high‐grade PIN as the most severe lesions in the anterior and dorsal lobes of the dutasteride groups increased and decreased, respectively. There was also an increased incidence of poorly differentiated cancer as the most severe lesion in the dorsal lobe of pre‐dutasteride and both finasteride groups. There are some commonalities between our findings and trial results reported previously.