First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN)

Background: Targeted pharmacological correction is used extensively in medical practice today. 3,3'-Diindolylmethane (DIM) is known as a substance with various anticancer properties. An interim study of the efficacy of a new drug Infemin on the basis of diindolylmethane (DIM) with improved bioavalability has been conducted. Methods: The clinical trial had a multicenter, randomized, placebo-controlled, double-blind design and was carried out in two parallel groups. The interim analysis of data included 21 patients diagnosed with a high-grade prostatic intraepithelial neoplasia (PIN). Group 1 (11 patients) received Infemin in a dose of 900 mg of DIM a day, and group 2 (10 patients) received placebo. To assess the efficacy of therapy, the analysis of morphological index (MI) changes based on the results of histological examinations of prostate biopsy specimens was performed, and a proportion of patients with persistent PIN in 12 months after Infemin initiation was calculated. Researchers also evaluated prostate size, urodynamic parameters (Qmax, Qave, Vres), IPSS, and QoL (quality of life) indices and International Index of Erectile Function (IIEF) at 3, 6, 9, and 12 months after the Infemin administration start. Results: After 12 months of treatment in the Infemin group, MI decreased from 0.50 to 0.08, while in the placebo group, it increased from 0.27 to 0.58; the difference between the groups was statistically significant (p = 0.0003, Mann-Whitney test). In 45.5 % of patients in the Infemin group, a complete regression of PIN was also observed, while in the placebo group, PIN regression was not observed in any patients (p = 0.053, Yates' corrected chi-square). Study results in the Infemin group show improvement of maximal urinary flow rate Qmax (53.3 % increase compared to the initial value); however, the statistical significance was not reached (p = 0.180, Mann-Whitney test) due to the small sample size. Evaluation of other urodynamic parameters, prostate volume, quality of life, symptoms reflecting urination disorder, and erectile dysfunction symptoms did not reveal significant differences between the Infemin and placebo groups either which is probably due to the small sample size. Conclusions: The intermediate results of the 21 patients in this multicenter, randomized, placebo-controlled, double-blind study show that Infemin may be a promising drug candidate in patients with high-grade PIN. © 2016 Paltsev et al.