The Nutritional Prevention of Cancer (NPC) Trial, a randomized, double-blind, Phase III clinical intervention trial of oral selenium (Se) supplementation, was designed to test the preventive chemo effects of Se on recurrence of non-melanoma skin cancer. A striking 63% reduction in prostate cancer incidence during the initial 10 years of follow- up was observed in the treatment group compared to the placebo group. An analysis of the last three years of the blinded phase of this study showed a significant decrease in prostate cancer incidence in participants within the lowest two tertiles of baseline plasma selenium levels. In these groups, the prostate cancer incidence after 13 years of follow-up was decreased by 86% and 67%, respectively, in the treatment group vs. placebo. Based on these striking results, the primary objective of this proposal is to continue and complete an ongoing randomized, double-blind, placebo-controlled Phase III clinical trial (the """"""""Negative Biopsy Study"""""""", R01 CA77789), designed to determine the safety and efficacy of daily oral Se supplementation as a chemo preventive regimen in men considered to be at high-risk for prostate cancer who have had at least one prostate biopsy negative for cancer or high-grade intraepithelial neoplasia (HGPIN). This will allow successful completion of this innovative study by providing continuous and necessary follow-up of participants currently on study, without disruption of supplementation and scheduled assessments. In addition, modulation of potentially predictive biomarkers of prostate cancer will be analyzed in prostate tissue collected from baseline and subsequent prostate biopsies. The safety profile of high-selenium yeast will also be further established. The hypothesis continuing to be tested in this competing renewal is that supplementation with the essential trace element selenium will decrease the incidence of prostate cancer and corresponding biomarker expression in high-risk men. The primary endpoint is the incidence of prostate cancer on subsequent prostate biopsy. Serum samples collected during this study are used to analyze serum prostate specific antigen (PSA) levels, and will provide a valuable resource for future serum proteomic analyses. Immunohistochemistry and analyses of nuclear chromatin patterns in prostate biopsy tissue will be studied as intermediate endpoint biomarkers of prostate cancer. ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Subcommittee G - Education (NCI)
Program Officer
Parnes, Howard L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Algotar, Amit M; Behnejad, Roxanna; Stratton, M Suzanne et al. (2014) Chronic use of NSAIDs and/or statins does not affect PSA or PSA velocity in men at high risk for prostate cancer. Cancer Epidemiol Biomarkers Prev 23:2196-8
Algotar, Amit Mohan; Hsu, Chui-Hseih; Singh, Parminder et al. (2013) Selenium supplementation has no effect on serum glucose levels in men at high risk of prostate cancer. J Diabetes 5:465-70
Algotar, Amit M; Stratton, M Suzanne; Ahmann, Frederick R et al. (2013) Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer. Prostate 73:328-35
Algotar, A M; Stratton, M S; Xu, M J et al. (2011) Dose-dependent effects of selenized yeast on total selenium levels in prostatic tissue of men with prostate cancer. Nutr Cancer 63:1-5
Han, Jun; Slate, Elizabeth H; Pena, Edsel A (2007) Parametric latent class joint model for a longitudinal biomarker and recurrent events. Stat Med 26:5285-302
Karunasinghe, Nishi; Ferguson, Lynnette R; Tuckey, John et al. (2006) Hemolysate thioredoxin reductase and glutathione peroxidase activities correlate with serum selenium in a group of New Zealand men at high prostate cancer risk. J Nutr 136:2232-5
Gonzalez, Juan R; Pena, Edsel A; Slate, Elizabeth H (2005) Modelling intervention effects after cancer relapses. Stat Med 24:3959-75
Karunasinghe, Nishi; Ryan, Jacqueline; Tuckey, John et al. (2004) DNA stability and serum selenium levels in a high-risk group for prostate cancer. Cancer Epidemiol Biomarkers Prev 13:391-7
Inoue, Lurdes Y T; Etzioni, Ruth; Slate, Elizabeth H et al. (2004) Combining longitudinal studies of PSA. Biostatistics 5:483-500
Meuillet, Emmanuelle; Stratton, Suzanne; Prasad Cherukuri, Durga et al. (2004) Chemoprevention of prostate cancer with selenium: an update on current clinical trials and preclinical findings. J Cell Biochem 91:443-58

Showing the most recent 10 out of 13 publications