A Phase II Randomized, Double-blind, Presurgical Trial of Polyphenon E in Bladder Cancer Patients to Evaluate Pharmacodynamics and Bladder Tissue Biomarkers

We performed a phase II pharmacodynamic prevention trial of Polyphenon E [a green tea polyphenol formulation primarily consisting of epigallocatechin gallate (EGCG)] in patients prior to bladder cancer surgery. Patients with a bladder tumor were randomized to receive Polyphenon E containing either 800 or 1,200 mg of EGCG or placebo for 14 to 28 days prior to transurethral resection of bladder tumor or cystectomy. The primary objective was to compare the postintervention EGCG tissue levels in patients receiving Polyphenon E as compared with placebo. Secondary objectives included assessments of tissue expression of PCNA, MMP2, clusterin, VEGF, p27, IGF-1, IGFBP-3; correlation of tissue, plasma, and urine levels of EGCG; and EGCG metabolism by catechol-O-methyltransferase and UDP-glucuronosyltransferase pharmacogenomic mutations. Thirty-one patients (male:female, 26:5; mean age, 67.2 years) were randomized and 29 (94%) completed the study. There was not an observed significant difference ( = 0.12) in EGCG tissue levels between two Polyphenon E dosage groups combined versus placebo. However, a dose-response relationship for EGCG levels was observed in both normal ( = 0.046) and malignant bladder tissue ( = 0.005) across the three study arms. In addition, EGCG levels in plasma ( < 0.001) and urine ( < 0.001) increased and PCNA ( = 0.016) and clusterin ( = 0.008) were downregulated in a dose-dependent fashion. No pharmacogenomic relationship was observed. EGCG levels in plasma, urine, and bladder tissue followed a dose-response relationship, as did modulation of tissue biomarkers of proliferation and apoptosis. Despite the limitations of this pilot study, the observed pharmacodynamics and desirable biologic activity warrant further clinical studies of this agent in bladder cancer prevention. .