Prostate Cancer Chemoprevention Study: An investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen

Our previous case-control study suggested that equol, a metabolite of isoflavone, has a preventive effect on prostate cancer. To examine the prostate cancer risk based on isoflavone intake and equol production, we carried out a phase II, randomized, double-blind, placebo-controlled trial of oral isoflavone (60mg/day) for 12months. The inclusion criteria were Japanese men between 50 and 75years of age, a serum prostate-specific antigen level of 2.5-10.0ng/mL, and a single, negative prostate biopsy within 12months prior to enrollment. The study included 158 men in eight Japanese centers. Their median age was 66.0years, and the numbers of equol producers and non-producers were 76 (48%) and 82 (52%), respectively. The majority of adverse events were mild or moderate in severity, and the scheduled intake of tablets was completed by 153 patients (96.8%). The prostate-specific antigen value showed no significant difference before and after treatment. Of the 89 patients evaluated by central pathological review, the incidence of biopsy-detectable prostate cancer in the isoflavone and placebo groups showed no significant difference (21.4%vs 34.0%, P=0.140). However, for the 53 patients aged 65years or more, the incidence of cancer in the isoflavone group was significantly lower than that in the placebo group (28.0%vs 57.1%, P=0.031). These results support the value of isoflavone for prostate cancer risk reduction. A large-scale phase III randomized study of isoflavone tablets in men with different hereditary factors and living environments is warranted. Registered with the UMIN Clinical Trials Registry (UMIN-CTR) for clinical trials in Japan (C000000446).