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

The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
The Prostate (Impact Factor: 3.57). 02/2013; 73(3). DOI: 10.1002/pros.22573
Source: PubMed


This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.

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 >0.75 ng/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 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model.

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).

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.

17 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Results of recent epidemiologic studies suggest the need to reassess the safe upper limit in drinking water of selenium, a metalloid with both toxicological and nutritional properties. Observational and experimental human studies on health effects of organic selenium compounds consumed through diet or supplements, and of inorganic selenium consumed through drinking water, have shown that human toxicity may occur at much lower levels than previously surmised. Evidence indicates that the chemical form of selenium strongly influences its toxicity, and that its biological activity may differ in different species, emphasizing the importance of the few human studies on health effects of the specific selenium compounds found in drinking water. Epidemiologic studies that investigated the effects of selenate, an inorganic selenium species commonly found in drinking water, together with evidence of toxicity of inorganic selenium at low levels in from in vitro and animal studies, indicate that health risks may occur at exposures below the current European Union and World Health Organization upper limit and guideline of 10 and 40μg/l, respectively, and suggest reduction to 1μg/l in order to adequately protect human health. Although few drinking waters are currently known to have selenium concentrations exceeding this level, the public health importance of this issue should not be overlooked, and further epidemiologic research is critically needed in this area.
    Science of The Total Environment 12/2012; 443C:633-642. DOI:10.1016/j.scitotenv.2012.11.025 · 4.10 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Scientific opinion on the relationship between selenium and the risk of cancer has undergone radical change over the years, with selenium first viewed as a possible carcinogen in the 1940s then as a possible cancer preventive agent in the 1960s-2000s. More recently, randomized controlled trials have found no effect on cancer risk but suggest possible low-dose dermatologic and endocrine toxicity, and animal studies indicate both carcinogenic and cancer-preventive effects. A growing body of evidence from human and laboratory studies indicates dramatically different biological effects of the various inorganic and organic chemical forms of selenium, which may explain apparent inconsistencies across studies. These chemical form-specific effects also have important implications for exposure and health risk assessment. Overall, available epidemiologic evidence suggests no cancer preventive effect of increased selenium intake in healthy individuals and possible increased risk of other diseases and disorders.
    Journal of Environmental Science and Health Part C Environmental Carcinogenesis & Ecotoxicology Reviews 10/2013; 31(4):305-41. DOI:10.1080/10590501.2013.844757 · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose of review: This article provides an update of clinical research supported by the National Cancer Institute's Phase I/II prostate cancer chemoprevention agent development program. Recent findings: Numerous clinical trials of pharmacologic interventions to delay, prevent or reverse carcinogenesis ('chemoprevention') with the ultimate goal of reducing cancer incidence have been conducted over the past decade. These trials range from relatively small, short-duration studies with biomarker endpoints to very large, long-term, general population trials with definitive cancer endpoints. Two large, population-based, Phase III prostate cancer prevention trials have shown a significant benefit for 5-α-reductase inhibitors. However, this class of agents was also associated with increased detection of high-grade prostate cancer. Another large, Phase III prostate cancer prevention trial showed no benefit for either selenium or vitamin E, given individually or in combination; in fact, a significant increase in prostate cancer was observed among men randomized to the vitamin E alone arm. Summary: A number of early phase trials and three definitive Phase III trials have been conducted in the field of prostate cancer prevention over the past decade. Although a great deal has been learned from these studies, significant work remains to be done to fully realize the potential of chemoprevention in this disease.
    Current opinion in oncology 03/2013; 25(3). DOI:10.1097/CCO.0b013e32835fc8d4 · 4.47 Impact Factor
Show more