Abstract
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
The Journal of urology, Vol.193(4S), pp.e293-e293
04/2015
DOI: 10.1016/j.juro.2015.02.1123
Abstract
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.
Details
- Title: Subtitle
- 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
- Creators
- Jason Gee - Burlington CollegeDaniel Saltzstein - Madison GroupKyungMann Kim - Madison GroupJill Kolesar - Madison GroupWei Huang - Madison GroupTom Havighurst - Madison GroupBarbara Wollmer - Madison GroupJeanne Stublaski - Madison GroupTracy Downs - Madison GroupHasan Mukhtar - Madison GroupMargaret House - Bethesda, MDHoward Parnes - Bethesda, MDHoward Bailey - Madison Group
- Resource Type
- Abstract
- Publication Details
- The Journal of urology, Vol.193(4S), pp.e293-e293
- Publisher
- ELSEVIER SCIENCE INC
- DOI
- 10.1016/j.juro.2015.02.1123
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Language
- English
- Date published
- 04/2015
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695799302771
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