A randomized phase ii study of pomegranate extract for men with rising psa following initial therapy for localized prostate cancer

ABSTRACT BACKGROUND: Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of

pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome. METHODS: This randomized, multi-center, double-blind phase II, dose-exploring

trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to

18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT

from baseline in each arm. RESULTS: Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (_P_<0.001). PSADT lengthened in the

low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (_P_=0.554). PSADT increases >100% of baseline

were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA

progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9%

and 13.5% of patients in the 1- and 3-g dose groups, respectively. CONCLUSIONS: POMx treatment was associated with ⩾6 month increases in PSADT in both treatment arms without adverse effects.

The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population. Access through your institution Buy or

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ACKNOWLEDGEMENTS We thank and appreciate the patients who participated in this study and the many nurses and other health-care providers who assisted with the study. We especially wish to

thank the efforts of Ting Wang, Serina King, Rana Sullivan and Susan Hudock at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Funding for this clinical trial and

investigational product were provided by POM Wonderful, LLC, and grant support was provided by an NCI Cancer Center Support Grant (P30) CA 006973. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS

* Prostate Cancer Research Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, C J Paller, X Ye & M A Carducci * Advanced Clinical Research Service,

Bannockburn, IL, USA P J Wozniak * POM Wonderful, Los Angeles, CA, USA B K Gillespie & H R Liker * Urological Associates of Lancaster, Lancaster, PA, USA P R Sieber * South Orange

County Medical Research Center, Laguna Hills, CA, USA R H Greengold * Lakeside Urology, St Joseph, MI, USA B R Stockton * The Urology Group, Cincinnati, OH, USA B L Hertzman * Accumed

Research Associates, Garden City, NY, USA M D Efros * Urology Enterprises, Marietta, GA, USA R P Roper * University of California, Los Angeles, CA, USA H R Liker Authors * C J Paller View

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author inPubMed Google Scholar * H R Liker View author publications You can also search for this author inPubMed Google Scholar * M A Carducci View author publications You can also search

for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to M A Carducci. ETHICS DECLARATIONS COMPETING INTERESTS The corresponding author, Michael Carducci, received

$1500 in 2007 from POM Wonderful, LLC, for participating in a discussion of future trials. Harley Liker and Patricia Wozniak are consultants to POM Wonderful, LLC, and Brad Gillespie was,

until 2011, the vice president of POM Wonderful. The remaining authors declare no conflict of interest. ADDITIONAL INFORMATION Registration: ClinicalTrials.Gov NCT01220817 RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Paller, C., Ye, X., Wozniak, P. _et al._ A randomized phase II study of pomegranate extract for men with rising PSA

following initial therapy for localized prostate cancer. _Prostate Cancer Prostatic Dis_ 16, 50–55 (2013). https://doi.org/10.1038/pcan.2012.20 Download citation * Received: 13 February 2012

* Revised: 24 April 2012 * Accepted: 29 April 2012 * Published: 12 June 2012 * Issue Date: March 2013 * DOI: https://doi.org/10.1038/pcan.2012.20 SHARE THIS ARTICLE Anyone you share the

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Nature SharedIt content-sharing initiative KEYWORDS * pomegranate * PSA recurrence * PSADT