Phase 3 clinical trial investigating the effect of selenium supplementation in men at high‐risk for prostate cancer

Abstract

Purpose This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer. Methods A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N =234), or 400 µg selenium (N=233) as selenized yeast. They were followed every six months for up five years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox-proportional hazards model. Result Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7] respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (p=0.18 and p=0.17, respectively). Conclusion Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention.

Prostate Cancer Prevention: Agent Development Strategies

“…With a median follow-up of 36 months no significant differences were seen in prostate cancer incidence: 11.3 % (placebo), 10.3 % (200 ug/day), and 10.0 % (400 ug/day), p = 0.86. In addition, the time to study endpoint was not different in the two selenium groups compared to the placebo group and the intervention had no effect on PSA velocity (Algotar et al 2013). These findings were compatible with the data from SELECT, the largest prostate cancer prevention trial conducted to date, in which selenium was administered in the form of selenomethionine rather than as high-selenium yeast (Lippman et al 2009;Klein et al 2011).…”

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study

“…The inadequacies in exposure assessment may have had a major role, in addition to confounding, in inducing the conflicting results of observational epidemiologic studies [7,8], which frequently failed to predict the recent and fairly consistent results of randomized controlled trials [10,[37][38][39][40][41] which have substantially changed the approach to the Se and cancer relation, and raised concern about the adverse health effects of this metalloid [3,12].…”

“…Results expressed as regression coefficient (ˇ), 95% confidence interval (CI) and P value (P). of speciation analyses, may have been a major source of exposure misclassification and thus explain the conflicting results of observational studies on the Se and cancer relation, as well as their partial failure in predicting the results of recent randomized trials [10,[37][38][39][40][41].…”

Chemoprevention of Prostate Cancer with the Polyamine Synthesis Inhibitor Difluoromethylornithine

“…Exciting new work with polyamine transport inhibitors has also refocused attention on the polyamine pathway (Samal et al 2013). Negative results in the large PCPT and SELECT trials (Thompson et al 2003;Algotar et al 2013) as well as the failure of toremifine and 1 a-hydroxyvitamin D2) (Gee et al 2013;Taneja et al 2013) in HGPIN has also refocused attention on DFMO. A wide ); p = 0.03…”