Abstract PR06: Effect of polyphenon E on progression to prostate cancer after diagnosis of high grade prostatic intraepithelial neoplasia
Authors: Kumar Nagi B. , Pow-Sang Julio , Egan Kathleen M. , Spiess Philippe A. , Dickinson Shohreh , Salup Raoul , Helal Mohamed , McLarty Jerry , Williams Christopher R. , Schreiber Fred , Sebti Said , Kazi Aslam , Kang Loveleen , Quinn Gwen , Smith Tiffany , Diaz Karen , Chornokur Ganna , Crocker Theresa , Schell Michael J. 
Published: October 2015

Abstract
Importance: In recent years, several studies have suggested effectiveness of green tea catechins in prostate cancer (PCa) chemoprevention. With the exception of one trial from Italy, this has not been further tested in a randomized trial setting in high-risk men with atypical small acinar proliferation (ASAP) or high grade prostatic intraepithelial neoplasia (HGPIN).
Objective: To determine whether the daily consumption of a standardized formulation of green tea catechins (Polyphenon E) supplement for 1 year reduces the rate of progression to PCa in men, diagnosed with HGPIN or ASAP. Additional objectives were to evaluate tolerance, lower urinary tract symptoms (LUTS) and quality of life (QOL).
Design, setting and participants: A randomized, double-blinded trial was conducted from September 2008 to March 2014 at medical centers in the US targeting 97 men diagnosed HGPIN or ASAP, randomized to treatment (n=49) or control arm (n=48). Supplement or placebo was initiated within 3 months of initial biopsy and continued for 1 year.
Intervention: Participants were block randomized by baseline diagnosis and study site to receive Polyphenon E (PolyE), a decaffeinated, standardized green tea catechin mixture, the main component of which is (−)-epigallocatechin-3-gallate (EGCG) at a dose of 400 mgs EGCG per day (200 mgs twice a day [BID]), or placebo.
Main outcomes and measures: Rate of progression to PCa at one year in men treated with PolyE or placebo following diagnosis of HGPIN or ASAP; evaluation of tolerance, LUTS and QOL.
Results: Overall, we did not observe a difference in the number of men who progressed to PCa in one year in the Poly E (4/49) arm compared to placebo arm(6/48). Secondary analyses of patients reaching a definitive endpoint revealed that among men with baseline diagnosis of HGPIN, a greater number progressed to ASAP or PCa in the placebo arm (10/25) compared to the PolyE arm (3/26; P&lt;0.05). Interestingly, this result was largely driven by the fact that a significantly greater number of subjects with baseline HGPIN progressed to ASAP in the placebo arm (5/25) compared to men in the PolyE arm (0/26; P &lt;0.05). In men with baseline diagnosis of ASAP, the rate of cancer diagnosis at the end of intervention were similar in both study arms. Men in the PolyE group treated for one year demonstrated a significant decrease in serum tPSA compared to those in the placebo group (-0.90 ng/mL;(95%CI:-1.67, -0.12; P&lt;0.05). No significant differences in tolerance, LUTS or QOL were observed between the two groups.
Conclusions and Relevance: Daily intake of a standardized, decaffeinated catechin mixture containing 400 mgs EGCG (200 mgs BID) for 1 year is well tolerated and appears to produce chemoprevention effects in the early stages (HGPIN to ASAP) of prostate carcinogenesis. These findings should be confirmed in a phase III clinical trial prior to recommending use in clinical settings.
Trial Registration: Clinical Trials.gov Identifier: NCT00596011
Acknowledgement: The research study was funded by the National Institute of Health- National Cancer Institute R01 CA12060-01A1. We acknowledge the contributions of Anthony M. Neuger, Domenico Coppola, Binglin Yue, (Moffitt Cancer Center); Kyle Anderson (Minneapolis VA Medical Center, Minneapolis, MN); Eduard Trabulsi (Jefferson Medical College, Philadelphia, PA); Tajammul Fazili (Overton Brooks VA, Shreveport, LA); Edward Giovanucci (Harvard University); Gregory Zagaja (University of Chicago, Chicago, IL); Shahnjayla Connors (University of Washington, St. Louis, MO); Folake Odedina (University of Florida). External Data Monitoring Board: Omer Kucuk, (Emory University), Phyllis Bowen (Retired), and Steven Clinton (Ohio State University).
Citation Format: Nagi B. Kumar, Julio Pow-Sang, Kathleen M. Egan, Philippe A. Spiess, Shohreh Dickinson, Raoul Salup, Mohamed Helal, Jerry McLarty, Christopher R. Williams, Fred Schreiber, Said Sebti, Aslam Kazi, Loveleen Kang, Gwen Quinn, Tiffany Smith, Karen Diaz, Ganna Chornokur, Theresa Crocker, Michael J. Schell. Effect of polyphenon E on progression to prostate cancer after diagnosis of high grade prostatic intraepithelial neoplasia. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PR06.