MP04-14 PHASE IIA, RANDOMIZED PLACEBO-CONTROLLED TRIAL OF SINGLE HIGH DOSE CHOLECALCIFEROL (VITAMIN D3) AND DAILY GENISTEIN (G-2535) VERSUS PLACEBO IN MEN WITH EARLY STAGE PROSTATE CANCER UNDERGOING PROSTATECTOMY

Abstract

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I1 Apr 2016MP04-14 PHASE IIA, RANDOMIZED PLACEBO-CONTROLLED TRIAL OF SINGLE HIGH DOSE CHOLECALCIFEROL (VITAMIN D3) AND DAILY GENISTEIN (G-2535) VERSUS PLACEBO IN MEN WITH EARLY STAGE PROSTATE CANCER UNDERGOING PROSTATECTOMY David F. Jarrard, Badrinath R. Konety, Joel Slaton, Wei Huang, Tracy Downs, Jill Kolesar, KyungMann Kim, Tom Havighurst, Margaret G. House, Howard L. Parnes, and Howard H. Bailey David F. JarrardDavid F. Jarrard More articles by this author , Badrinath R. KonetyBadrinath R. Konety More articles by this author , Joel SlatonJoel Slaton More articles by this author , Wei HuangWei Huang More articles by this author , Tracy DownsTracy Downs More articles by this author , Jill KolesarJill Kolesar More articles by this author , KyungMann KimKyungMann Kim More articles by this author , Tom HavighurstTom Havighurst More articles by this author , Margaret G. HouseMargaret G. House More articles by this author , Howard L. ParnesHoward L. Parnes More articles by this author , and Howard H. BaileyHoward H. Bailey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1949AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) represents an important target for chemoprevention given its prolonged natural history and predilection for afflicting an older population. Epidemiologic and laboratory data suggest that vitamin D and genistein (soy) in decreasing PCa progression. The effect of vitamin D on prostate epithelial cell proliferation and differentiation is well documented and genistein may augment this affect through inhibition of the CYP24 enzyme, which is responsible for intracellular vitamin D metabolism. In addition, both genistein and vitamin D inhibit the intraprostatic synthesis of prostaglandin E2, an important mediator of inflammation. In the current prospective, multicenter trial in patients undergoing radical prostatectomy for localized prostate cancer, the safety and effect of adding genistein to patients receiving a single, large dose of cholecalciferol was assessed. METHODS Men undergoing radical prostatectomy were randomly assigned to one of two treatment groups: (1) cholecalciferol: 200,000 IU as one dose at study entry plus genistein: 600 mg daily or (2) placebo cholecalciferol day 1 and placebo genistein PO daily for 21-28 days prior to radical prostatectomy. Serum and tissue analyses were performed and side-effects recorded. RESULTS A total of 15 patients were enrolled, 8 in the placebo arm and 7 in the vitamin D + genistein (VD+G) arm. All patients were compliant and completed the study. No significant differences in side effect profiles were noted. Utilization of the VD+G showed a trend toward increased calcitriol serum concentrations when compared to placebo (0.104 +/- 0.1 vs. 0.0013 +/-0.07; p=0.08); however, prostate tissue levels did not increase. Immunohistochemistry for marker analyses using VECTRA automated quantitation revealed a significant increase in AR expression (p=0.04) and a trend toward increased TUNEL staining (p=0.1) in prostate cancer tissues in men randomized to receive VD+G compared to placebo. CONCLUSIONS In this first study testing the combination of a single, large dose of cholecalciferol (200,000IU) and daily genistein (G-2535) the agents were well tolerated. While serum levels of calcitriol were increased on the intervention arm, prostate tissue levels were not. Increased prostatic AR expression (suggesting increased differentiation) and a trend toward increased TUNEL staining (increased apoptosis) were observed among men randomized to the combination. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e33-e34 Advertisement Copyright & Permissions© 2016MetricsAuthor Information David F. Jarrard More articles by this author Badrinath R. Konety More articles by this author Joel Slaton More articles by this author Wei Huang More articles by this author Tracy Downs More articles by this author Jill Kolesar More articles by this author KyungMann Kim More articles by this author Tom Havighurst More articles by this author Margaret G. House More articles by this author Howard L. Parnes More articles by this author Howard H. Bailey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...