Effect of the dual 5α-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer

Purpose: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5alpha-reductase (5alphaR) types 1 and 2 (5aR1 and 5aR2). Suppression of DHT formation by 5aR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5aR2 is the dominant enzyme in the prostate, evidence indicates that 5aR1 may be up-regulated in some prostate cancers. This suggests that dual inhibition of both isoenzymes may be more effective than suppression of 5aR2 alone in prostate cancer treatment or prevention. In this short-term pilot study we examined the effect of the dual 5aR inhibitor dutasteride on markers of tumor regression. Materials and Methods: A total of 46 men with clinically staged T1 or T2 prostate cancer were randomized to receive 5 mg per day of placebo or dutasteride for 6 to 10 weeks before radical prostatectomy. Resected tissues were analyzed to determine the effect of dutasteride on intraprostatic androgen levels, and indices of apoptosis and microvessel density (MVD) in malignant tissue, as well as degree of atrophy in benign tissue. Results: Treatment with dutasteride caused a 97% decrease in intraprostatic DHT and was associated with a trend toward increased apoptosis. In patients receiving dutasteride for 45 days or more, a significant increase in apoptosis and a trend toward decreased M-VD in prostate cancer tissue was observed. Dutasteride treatment was also associated with an 18% decrease in mean benign epithelial cell width compared with placebo (p <0.0001). Conclusions: In this pilot study dutasteride treatment resulted in almost complete suppression of intraprostatic DHT, increased apoptosis and a trend toward decreased M-VD. These findings suggest that short-term treatment with dutasteride can cause regression in some prostate cancers.