MP26-01 A PHASE II RANDOMIZED, PRESURGICAL PLACEBO-CONTROLLED TRIAL OF POLYPHENON E IN BLADDER CANCER PATIENTS TO EVALUATE BLADDER TISSUE LEVELS OF EGCG AND BIOMARKERS OF GROWTH AND APOPTOSIS (2015)

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2015MP26-01 A PHASE II RANDOMIZED, PRESURGICAL PLACEBO-CONTROLLED TRIAL OF POLYPHENON E IN BLADDER CANCER PATIENTS TO EVALUATE BLADDER TISSUE LEVELS OF EGCG AND BIOMARKERS OF GROWTH AND APOPTOSIS Jason Gee, Daniel Saltzstein, KyungMann Kim, Jill Kolesar, Wei Huang, Tom Havighurst, Barbara Wollmer, Jeanne Stublaski, Tracy Downs, Hasan Mukhtar, Margaret House, Howard Parnes, and Howard Bailey Jason GeeJason Gee , Daniel SaltzsteinDaniel Saltzstein , KyungMann KimKyungMann Kim , Jill KolesarJill Kolesar , Wei HuangWei Huang , Tom HavighurstTom Havighurst , Barbara WollmerBarbara Wollmer , Jeanne StublaskiJeanne Stublaski , Tracy DownsTracy Downs , Hasan MukhtarHasan Mukhtar , Margaret HouseMargaret House , Howard ParnesHoward Parnes , and Howard BaileyHoward Bailey View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1123AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Green tea consumption has been associated with a reduction in bladder cancer risk. Polyphenon E is a green tea polyphenol formulation primarily consisting of epigallocatechin gallate (EGCG) which in preclinical studies inhibits the growth of bladder cancer. We evaluated the tolerability, tissue accumulation, and biologic effects of polyphenon E in patients with bladder cancer. METHODS Patients with a bladder tumor found on cystoscopy were randomized in a 1:1:1 ratio to receive 800 mg, 1200 mg or placebo polyphenon E prior to TURBT or radical cystectomy. The primary study objective was to assess the nonmalignant bladder tissue levels of EGCG. Secondary objectives included EGCG levels in benign versus malignant tissue; tissue expression of PCNA, MMP2, Clusterin, VEGF, p27, IGF-1, & IGFBP-3; correlation of plasma, urine and tissue levels of EGCG as well as other catechins (epicatechin, epicatechin gallate, and epigallocatechin); metabolism of EGCG in plasma, urine and tissue by COMT and UGT in relation to pharmacogenomic mutations. RESULTS 31 patients (84% male, 16% female) were randomized with a mean age of 67.2 years, whereby 24 (77%) completed study agent administration. Adverse events were severe for one (3%) patient, moderate for five patients (16%), and mild for eight (26%) patients. Although with a low rate of detectability in tissue (4/25), dose-dependent levels of EGCG were observed in normal (0.00, 0.50, 1.72 ng/ml, p=0.046) and malignant (0.00, 0.00, 2.54 ng/ml p=0.005) bladder tissue for the placebo, low dose and high dose polyphenon E arms respectively. Plasma EGCG levels (2.94, 78.09, 87.52 ng/ml, p=0.001) and urine EGCG levels (0.00, 2.60, 4.32 ng/ml, p<0.001) were also dose-dependent, as well as the downregulation of tissue biomarkers PCNA (0.41, 0.38, 0.35 OD, p=0.016) and clusterin (0.074, 0.061, 0.046 OD, p=0.008), with a nonsignificant reduction in p27 (0.36, 0.35, 0.31 OD, p=0.15). No consistent pharmacogenomic relationship was observed. CONCLUSIONS We demonstrate tissue accumulation of EGCG in benign and malignant bladder urothelium which follows plasma and urine levels in a dose-dependent fashion. Furthermore, tissue biomarkers of proliferation (PCNA) and apoptosis (clusterin) were reduced in a dose-dependent fashion. Acknowledging the limitations of this pilot study, definable tissue accumulation of polyphenon E, as well as desirable biologic activity warrant further clinical studies of this agent on actual bladder tumor recurrence and progression. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e293 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Gee More articles by this author Daniel Saltzstein More articles by this author KyungMann Kim More articles by this author Jill Kolesar More articles by this author Wei Huang More articles by this author Tom Havighurst More articles by this author Barbara Wollmer More articles by this author Jeanne Stublaski More articles by this author Tracy Downs More articles by this author Hasan Mukhtar More articles by this author Margaret House More articles by this author Howard Parnes More articles by this author Howard Bailey More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...