Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures

Abstract

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers Copyright: © 2012 Kumar N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Conflict of Interest:To date, the results of this study in part or as a whole has not been reported nor presented elsewhere. Disclaimers:The authors disclose no conflict of interest. NIH Public Access Prostate Cancer ChemopreventionChemoprevention refers to the inhibition of preinvasive and invasive cancer and its progression or treatments of identifiable precancers [8,15]. Chemoprevention efforts require a thorough understanding of the mechanism of carcinogenesis including signaling and metabolic pathways and genetic progression pathways. Agent Selection and DescriptionEGCG is the major and most active catechin in green tea and is the most commonly studied GTC in vitro, because of its relative abundance in green tea extracts and strong cancer preventative properties [20][21][22]. However, EGCG has low rates of absorption and bioavailability when administered orally [23][24][25] and studies indicate that whole mixtures of GTCs may more accurately reflect the human consumption of green tea. This is possibly due to the fact that tea constituents other than catechins may also have anti-carcinogenetic activity and the combined interaction of tea components and catechins may contribute to the effectiveness of the anticarcinogenic activities of GTC mixtures [25][26][27][28][29]. The lack of assurance of infusion contents, differences in tea origin and brewing techniques, all which affect the tea catechin content, have made it necessary to use more standardized GTC mixtures for clinical purposes [30].Based on the safety profile established in phase I clinical trials [24,31,32], we selected a standardized decaffeinated botanical formulation of green tea catechins, Polyphenon E (Mitsui Norin Co., Ltd., Shizuoka, Japan; Mitsui Norin) for use in this clinical trial. Polyphenon E, is a botanical drug substance containing a mixture of catechins originating from the leaves of green tea (Camellia sinensis). The final product contains 85-95% total catechins; the main component is EGCG, which comprises 5...

Chemoprevention in African American Men with Prostate Cancer

“…Based on the results of previous studies, a placebocontrolled, randomized clinical trial was conducted of the high-grade green tea extract in 97 men with HG-PIN, atypical small acinar proliferation, or both conditions. 64,92,[119][120][121] No differences were observed in the number of prostate cancer cases. The cumulative rate of prostate cancer plus atypical small acinar proliferation among men with HGPIN but without atypical small acinar proliferation at the start of the study was researched.…”

“…Randomized placebo control trials and the longterm follow-up and monitoring of patients and study participants are critical to meet the requirements of the US Food and Drug Association and to promote the acceptance of new agents into the marketplace. 92,93…”

Green Tea and Its Extracts in Cancer Prevention and Treatment

“…Kumar et al [203] proposed a design for clinical trials. They argue that pharmacology data for neutraceuticals like Polyphenon E and food supplements like GT should be included in any study protocol, as well as for extending these studies to realistic clinical time scenarios relevant for tumor progression (i.e., 5 to 20 years observation).…”

A Perspective on Prostate Carcinogenesis and Chemoprevention

“…We did not find protective activity of green tea extract on chemical-hormonal induction of prostate cancer in rats (unpublished results). Although more clinical studies are ongoing [95], it seems unlikely at present that green tea provides a substantive amount of protection against prostate cancer development.…”