TY - JOUR
T1 - A phase II randomized, double-blind, presurgical trial of polyphenon e in bladder cancer patients to evaluate pharmacodynamics and bladder tissue biomarkers
AU - Gee, Jason R.
AU - Saltzstein, Daniel R.
AU - Kim, Kyung Mann
AU - Kolesar, Jill
AU - Huang, Wei
AU - Havighurst, Thomas C.
AU - Wollmer, Barbara W.
AU - Stublaski, Jeanne
AU - Downs, Tracy
AU - Mukhtar, Hasan
AU - House, Margaret G.
AU - Parnes, Howard L.
AU - Bailey, Howard H.
N1 - Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/5
Y1 - 2017/5
N2 - 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 (P = 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 (P = 0.046) and malignant bladder tissue (P = 0.005) across the three study arms. In addition, EGCG levels in plasma (P < 0.001) and urine (P < 0.001) increased and PCNA (P = 0.016) and clusterin (P = 0.008) were downregulated in a dosedependent 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.
AB - 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 (P = 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 (P = 0.046) and malignant bladder tissue (P = 0.005) across the three study arms. In addition, EGCG levels in plasma (P < 0.001) and urine (P < 0.001) increased and PCNA (P = 0.016) and clusterin (P = 0.008) were downregulated in a dosedependent 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.
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U2 - 10.1158/1940-6207.CAPR-16-0167
DO - 10.1158/1940-6207.CAPR-16-0167
M3 - Article
C2 - 28325826
AN - SCOPUS:85019617419
SN - 1940-6207
VL - 10
SP - 298
EP - 307
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 5
ER -