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.

Trial registration: ClinicalTrials.gov NCT01220817.

Conflict of interest statement

CONFLICT OF INTEREST

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.

Figures

Figure 1

PSADT percentage change from baseline for each patient in the 1-POMx and 3-POMx treatment groups. (Notes: (1) Patients with negative baseline PSADT were excluded, (2) Patients with negative post-baseline PSADT were assigned the largest observed post-baseline PSADT and (3) Six 1-POMx and nine 3-POMx subjects had PSADT percentage change from baseline >1000%). POMx, pomegranate extract; PSADT, PSA doubling time.

Figure 2

Number of subjects in each post-baseline PSA doubling time (PSADT) range grouped by baseline PSADT range.