Abstract BACKGROUND: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. Data from preclinical models strongly support epidermal growth factor receptor (EGFR) as a target for chemoprevention of HCC. Erlotinib is a small-molecular EGFR tyrosine kinase inhibitor that is FDA-approved for cancer treatment. The side effects of erlotinib observed in patients receiving the oncology dose (150 mg/day) render it unacceptable as a chemoprevention agent at this dose. OBJECTIVE: The objective of this clinical trial was determination of a safe and minimum effective dose of erlortinib for which a ≥50% reduction phospho-EGFR immunohistochemical staining in the liver was observed. RESULTS: 46 participants were pre-registered and 25 participants were registered in this multicenter trial. In a dose de-escalation trial design, cohorts of participants received a 7 day course of erlotinib 75 mg/day, 50 mg/day or 25 mg/day with liver tissue acquisition prior to and after erlotinib. A ≥50% reduction phospho-EGFR immunohistochemical staining in the liver was observed in a minimum of 40% of participants at each of the dose levels. Erlotinib was very well tolerated with few side effects observed, particularly at the dose of 25 mg/day. A favorable modulation of the Prognostic Liver Signature was observed in participants that received the higher erlotinib doses (50 and 75 mg/day). CONCLUSION: These data support the selection a dose of 25 mg/day of erlotinib for a longer intervention to assess for evidence of efficacy as an HCC chemoprevention drug. Citation Format: Kenneth K. Tanabe, David Zahrieh, Carrie A. Strand, Yujin Hoshida, Thomas J. Flotte, Gary Della’Zanna, Asad Umar, Paul Limburg. Pilot study of EGFR inhibition with erlotinib in liver fibrosis for hepatocellular carcinoma prevention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3031.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Abstract Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2–5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.