Muscadine Grape Skin Extract in Men with Biochemically Recurrent Prostate Cancer: A Randomized, Multicenter, Placebo-Controlled Clinical Trial

Purpose: MPX, a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer (PCa) wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multi-center, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR PCa, powered to detect a prostate specific antigen doubling time (PSADT) difference of 6 months (low-dose) and 12 months (high-dose) relative to placebo. Participants were stratified (baseline PSADT, Gleason score) and randomly assigned 1:2:2 to receive placebo, 500mg MPX (low), 4000mg MPX (high) daily. Correlates included superoxide dismutase-2 (SOD2) genotype, lipid peroxidation and polyphenol pharmacokinetics. Results: The evaluable population included 112 patients, all treated for at least 6 months and 62% treated for 12 months. No significant difference was found in PSADT change between control and treatment arms (p=0.81): control 0.9 months (n=20, range -6.7 to 83.1), low-dose 1.5 months (n=52, range: -10.3 to 87.2), high-dose 0.9 months (n=40, range: -27.3 to 88.1). One high-dose patient experienced objective response. No drug-related CTCAE grade 3-4 adverse events were seen. In a preplanned exploratory analysis, PSADT pre-to-post increase was significant in the 27 (26%) genotyped patients with SOD2 Alanine/Alanine genotype (rs4880 T>C polymorphism) on MPX (pooled treatment arms) (6.4 months, p=0.02), but not in control (1.8 months, p=0.25). Conclusions: Compared with placebo, MPX did not significantly prolong PSADT in BCR patients over two different doses. Exploratory analysis revealed a patient population with potential benefit that would require further study.

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