title: Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus.
abstract: 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.
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York. akj3@cumc.columbia.edu.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Joe
authors.affiliation: Department of Medicine, Weill Cornell Medical Center, New York.
authors.forename: Felice
authors.initials: F
authors.lastname: Schnoll-Sussman
authors.affiliation: Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bresalier
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Abrams
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York.
authors.forename: Hanina
authors.initials: H
authors.lastname: Hibshoosh
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Ken
authors.initials: K
authors.lastname: Cheung
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Friedman
authors.affiliation: Department of Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University, Brentwood, Tennessee.
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Kazeem
authors.initials: K
authors.lastname: Abdul
authors.affiliation: Department of Medicine, Weill Cornell Medical Center, New York.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bigg
authors.affiliation: Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jessica
authors.initials: J
authors.lastname: Foreman
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
authors.forename: Aqeel
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York.
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Esther
authors.initials: E
authors.lastname: Akpa
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Perloff
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Powel H
authors.initials: PH
authors.lastname: Brown
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lightdale
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000188:drug therapy*; D001706:Biopsy; D002392:Catechin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004945:Esophagoscopy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy / Q000379:methods*
chemical_list: D002392:Catechin; C045651:epigallocatechin gallate; C472086:polyphenon E