Purpose: MuscadinePlus (MPX), a commercial preparation of pulverized muscadine grape skin, was evaluated as a therapeutic option for men with biochemically recurrent (BCR) prostate cancer wishing to defer androgen deprivation therapy. Experimental Design: This was a 12-month, multicenter, placebo-controlled, two-dose, double-blinded trial of MPX in 125 men with BCR prostate cancer, powered to detect a PSA 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, 500 mg MPX (low), or 4, 000 mg 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, 6.7-83.1), low dose 1.5 months (n=52; range, 10.3-87.2), high dose 0.9 months (n = 40; range, 27.3-88.1). 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.
Bibliographical noteFunding Information:
This study was conducted within the Department of Defense/Prostate Cancer Foundation Prostate Cancer Clinical Trials Consortium (PCCTC). We thank the patients who volunteered to participate in this study, and their families. We are grateful to all the study staff members at each site, the research nurses, and the pharmacy staff. The project was supported by an ASCO YIA, ECOG Paul Carbone Fellowship, and a grant from the Community Foundation of the National Capital Region, as well as the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH grants P30 CA006973 and UL1 TR 001079, and the Shared Instrument Grant (1S10RR026824-01). The study drug was provided, at no cost, by Muscadine Naturals, Inc.
© 2017 AACR.