Prostate cancer is now the most common non-skin tumor in American men. The available therapeutic modalities for clinically organ- confined prostate cancer are limited, and effective therapies do not exist for metastatic disease. However, some compounds, such as antioxidants, have shown evidence that they may help prevent prostate cancer. Therefore, it is logical to implement chemoprevention trials of such potential chemopreventive agents with low toxicity that effectively reduces the incidence of cancer in high-risk populations. However, because of the lengthy and unpredictable natural history of prostate cancer, implementing a primary chemoprevention trial is logistically difficult. As such, it is logical to identify converging intermediate biomarkers (e.g., cellular, molecular, and genetic events) in a particular mechanistic pathway in a target population of men at high-risk of developing prostate cancer, with premalignant disease, or with low volume/low grade clinically organ-confined prostate cancer. Such intermediate biomarkers can serve as surrogate end points for a reduction in the cancer incidence in large randomized trials. Unfortunately, there is no established clinical model available to test the biologic activity of chemopreventive agents by measuring the effect of such agents on the pharmacodynamic modulatory effects on select biomarkers. This lack of a clinical model has slowed development of chemopreventive agents. We, therefore, propose to establish a clinical model in prostatic tissue sampling to determine biologic activity of select chemopreventive agents in the continuum of histologic changes in the prostate, which may reflect sequential molecular, genetic, and cellular events of carcinogenesis. To these ends, we will conduct a randomized, placebo-controlled short-term trial of d- alpha-tocopherol, 1-selenomethionine and the combination of d- alpha-tocopherol plus 1-selenomenthionine in presurgical cohorts with clinically organ-confined adenocarcinoma of the prostate.
| Tsavachidou, Dimitra; McDonnell, Timothy J; Wen, Sijin et al. (2009) Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst 101:306-20 |
| Kim, Jeri; Sun, Peiyu; Lam, Ying-Wai et al. (2005) Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer. Cancer Epidemiol Biomarkers Prev 14:1697-702 |
