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Basic Research

A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer

Abstract

Background:

The primary objective of this study was to compare the effects of pomegranate juice on PSA doubling times (PSADT) in subjects with rising PSA levels after primary therapy for prostate cancer.

Methods:

Double-blind, placebo-controlled multi-institutional study, evaluated the effects of pomegranate liquid extract on serum PSA levels. The primary end point of this study was change in serum PSADT. Additional secondary and exploratory objectives were to evaluate the safety of pomegranate juice and to determine the interaction of manganese superoxide dismutase (MnSOD) AA genotype and pomegranate treatment on PSADT.

Results:

One-hundred eighty-three eligible subjects were randomly assigned to the active and placebo groups with a ratio of 2:1 (extract N=102; placebo N=64; juice N=17). The majority of adverse events were of moderate or mild grade. Median PSADT increased from 11.1 months at baseline to 15.6 months in the placebo group (P<0.001) compared with an increase from 12.9 months at baseline to 14.5 months in the extract group (P=0.13) and an increase from 12.7 at baseline to 20.3 in the juice group (P=0.004). However, none of these changes were statistically significant between the three groups (P>0.05). Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P=0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P=0.03).

Conclusions:

Compared with placebo, pomegranate extract did not significantly prolong PSADT in prostate cancer patients with rising PSA after primary therapy. A significant prolongation in PSADT was observed in both the treatment and placebo arms. Men with the MnSOD AA genotype may represent a group that is more sensitive to the antiproliferative effects of pomegranate on PSADT; however, this finding requires prospective hypothesis testing and validation.

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Acknowledgements

Study funding, pomegranate products and placebos provided by Pom Wonderful. Manuscript co-author AJP has received research funding from and DH has received research funding and is a paid consultant to Pom Wonderful. Study Principal Investigators include: RD (Taussig Cancer Center Cleveland Clinic), AK (Winthrop Medical Center), AJP (UCLA Institute of Urologic Oncology), JC (Virginia Mason Medical Center), CAP (University of Texas MD Anderson Cancer Center), Sheldon Freedman, Gary Karlin (AdvanceMed Research), WA (UCLA, West LA VAMC), Giribala Patel (St Jude Heritage Medical Group), Andre Liem (Pacific Shores Medical Group), Frederic Kass (Santa Barbara Hematology Oncology Group), Robert Dichman (Central Coast Medical Oncology Corporation), Brad Bauer (Alabama Clinical Research Institute), WC (Alaska Clinical Research Center), GS (Five Valleys Urology), Ron Israeli (Staten Island Urologic Research), Joseph Kuntze (Coastal Medical Research Group), Robert Kratzke (University of Minnesota). Contract Research Organization (CRO) clinical trial support services provided by Radiant Clinical Research, Chicago, IL, USA. Data management and statistical analysis performed by Daniela Markovic and Jeffrey Gornbein, PhD, from the UCLA Department of Biomathematics.

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Correspondence to A J Pantuck.

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Competing interests

Manuscript co-author AJP has received research funding from and DH has received research funding and is a paid consultant to Pom Wonderful. The remaining authors declare no conflict of interest.

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Pantuck, A., Pettaway, C., Dreicer, R. et al. A randomized, double-blind, placebo-controlled study of the effects of pomegranate extract on rising PSA levels in men following primary therapy for prostate cancer. Prostate Cancer Prostatic Dis 18, 242–248 (2015). https://doi.org/10.1038/pcan.2015.32

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