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A phase I dose escalation study of Polyphenon E in liver cirrhosis: Evaluation of safety and effect on liver γ-OHPdG levels.

About this Publication
Title
A phase I dose escalation study of Polyphenon E in liver cirrhosis: Evaluation of safety and effect on liver γ-OHPdG levels.
Pubmed ID
40574339 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Cancer Prev Res (Phila). 2025 Jun 27
Authors
He AR , Smith CI , Cruz-Correa M , Chakraborty R , Zhang S , Sang S , Cheng G , Hecht SS , Bazzi LA , Kocherginsky M , Benante KA , Schering T , Richmond E , Rodriguez LM , Khan SA , Chung FL
Affiliations
  • Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, United States.
  • MedStar Georgetown University Hospital, United States.
  • University of Puerto Rico, Medical Sciences Campus, San Juan, PR, Puerto Rico.
  • Georgetown University Medical Center, United States.
  • North Carolina A&T State University, Kannapolis, North Carolina, United States.
  • North Carolina Agricultural and Technical State University, Kannapolis, United States.
  • University of Minnesota, Minneapolis, MN, United States.
  • Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
  • Northwestern University Feinberg School of Medicine, Chicago, Il, United States.
  • Northwestern University, Chicago, IL, United States.
...show more
  • National Cancer Institute, Bethesda, MD, United States.
  • National Cancer Institute, Rockville, md, United States.
  • Georgetown University, Washington, DC, United States.
Abstract

Accumulation of the DNA adduct γ-hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG) is associated with HCC development. Theaphenon E-a green tea polyphenol extract dosed according to mg of epigallocatechin gallate (EGCG)-suppresses the formation of γ-OHPdG and reduces hepatocellular carcinoma (HCC) development in preclinical models. This study aimed to evaluate the safety of Polyphenon E (Theaphenon E equivalent) and its effect on liver γ-OHPdG levels in patients with cirrhosis. This Phase I trial used a 3 + 3 dose escalation design with five planned Polyphenon E (EGCG) dose levels: 400 mg, 800 mg, 1200 mg, 1600 mg, and 2000 mg daily, administered orally for 24 weeks. Each dose cohort was monitored for "discontinue therapy" criteria for four weeks before additional participants were enrolled in the next cohort. Participant liver samples were assessed for γ-OHPdG levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and vibration-controlled transient elastography (VCTE); endogenous catechin pharmacokinetic (PK) data were analyzed. Grade 1 and 2 treatment-related adverse events (AEs) were observed in 38% of participants. Liver γ-OHPdG levels declined after treatment in most participants. There was a decrease in the VCTE-controlled attenuation parameter in some participants. After Polyphenon E dosing, the catechin PK clearance patterns were equivalent for all doses except 1600 mg. Polyphenon E was well tolerated in participants with cirrhosis at a dose up to and including 1600 mg/day. Therefore, the recommended starting dose for a phase II trial in a cirrhotic population is 1200 mg. We observed promising Polyphenon E suppression of liver OHPdG levels.

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