A phase IIa randomized placebo-controlled trial of pomegranate fruit extract/POMx in subjects with clinically localized prostate cancer undergoing active surveillance.

Abstract

285 Background: Due to its high prevalence and often indolent natural history, prostate cancer(PC) active surveillance(AS) is an ideal setting for chemoprevention. Studies assessing pomegranate and its extracts have shown promising anti-proliferative and pro-apoptotic effects in cell lines and animal models and a single-arm clinical trial of pomegranate fruit extract(PFE) reported an increase in PSA doubling time(PSADT) during AS. The primary objective of this trial was to assess the effect of PFE supplementation on plasma levels of Insulin-like Growth Factor-1(IGF-1). Secondary objectives addressed PSA doubling time(PSADT), tumor volume on end-of-study(EOS) biopsy and plasma and prostate tissue biomarkers. Methods: Men with organ-confined favorable-risk PC on AS were randomly assigned to receive PFE 1,000 mg(n=15) or placebo(n=15) once daily for twelve months. Prostate biopsies were performed at study entry and upon completion of the one-year intervention. Tissue biomarkers were assessed by immunohistochemistry(IHC) with automated quantitation. Results: PFE was well-tolerated with no significant toxicities. One patient withdrew before study initiation and 29 completed the one-year intervention. No differences in plasma IGF-1 levels(p=0.5), PSADT, or tissue biomarkers of apoptosis or proliferation were observed. A significant increase in urolithin A(a urinary metabolite of pomegranate) was observed in the PFE arm. IHC analyses of both tumor (Table) and normal-appearing tissue adjacent to tumor showed reductions from baseline in IGF-1, 8-OHdG(DNA damage marker), and androgen receptor expression associated with PFE treatment. A trend towards a reduction in the maximum percent of biopsy core tumor involvement was observed(p=0.06) in PFE. Conclusions: PFE administration for 12-months was not associated with a decrease in plasma IGF-1 levels nor an increase in PSADT. However, exploratory analyses suggest that PFE may contain bioactive compounds capable of altering biomarkers in PC and normal-appearing adjacent tissue providing a rationale for further investigation of PFE in the active surveillance population.