Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus

作者：Joe Andrew K^*; Schnoll Sussman Felice; Bresalier Robert S; Abrams Julian A; Hibshoosh Hanina; Cheung Ken; Friedman Richard A; Yang Chung S; Milne Ginger L; Liu Diane D; Lee J Jack; Abdul Kazeem; Bigg Michelle; Foreman Jessica; Su Tao; Wang Xiaomei; Ahmed Aqeel; Neugut Alfred I; Akpa Esther; Lippman Scott M; Perloff Marjorie; Brown Powel H; Lightdale Charles J

来源：Cancer Prevention Research, 2015, 8(12): 1131-1137.

DOI：10.1158/1940-6207.CAPR-14-0274-T

This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level-mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa.

• 出版日期2015-12