TY - JOUR
T1 - Phase ib randomized, Double-blinded, Placebo- Controlled, Dose escalation study of polyphenon e in patients with barrett's esophagus
AU - Joe, Andrew K.
AU - Schnoll-Sussman, Felice
AU - Bresalier, Robert S.
AU - Abrams, Julian A.
AU - Hibshoosh, Hanina
AU - Cheung, Ken
AU - Friedman, Richard A.
AU - S.yang, Chung
AU - Milne, Ginger L.
AU - Liu, Diane D.
AU - Lee, J. Jack
AU - Abdul, Kazeem
AU - Bigg, Michelle
AU - Foreman, Jessica
AU - Su, Tao
AU - Wang, Xiaomei
AU - Ahmed, Aqeel
AU - Neugut, Alfred I.
AU - Akpa, Esther
AU - Lippman, Scott M.
AU - Perloff, Marjorie
AU - Brown, Powel H.
AU - Lightdale, Charles J.
N1 - Publisher Copyright:
© 2015 American Association for Cancer Research.
PY - 2015/12
Y1 - 2015/12
N2 - 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 welltolerated, 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.
AB - 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 welltolerated, 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.
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U2 - 10.1158/1940-6207.CAPR-14-0274-T
DO - 10.1158/1940-6207.CAPR-14-0274-T
M3 - Article
C2 - 26471236
AN - SCOPUS:84951952332
SN - 1940-6207
VL - 8
SP - 1131
EP - 1137
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 12
ER -