High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation

Transpl Int. 2012 Nov;25(11):1158-64. doi: 10.1111/j.1432-2277.2012.01540.x. Epub 2012 Aug 6.

Abstract

Treatment options of recurrent hepatocellular carcinoma (HCC) after liver transplantation are limited and data on systemic compounds for advanced tumor stages in transplant recipients are sparse. We retrospectively analyzed the toxicity, tolerability, and efficacy of sorafenib in combination with mTOR inhibitors (mTORi), or calcineurin inhibitors (CNI) in transplant recipients with recurrent HCC. In total, 20 of 92 patients transplanted for HCC within a 10-year time period, experienced tumor recurrence. In case of ineligibility for other treatment options, patients received sorafenib (n = 13). In addition, CNI were stopped and switched to mTORi in nine patients, whereas CNI were continued in four patients. Grade 3-4 adverse events were observed in 92% of all patients necessitating sorafenib discontinuation in 77%. The most common severe adverse events were acute hepatitis, diarrhea, hand-foot - skin reaction and bone marrow suppression. In patients receiving sorafenib/mTORi one patient achieved partial response, and four achieved stable disease. In this cohort of liver transplant recipients side effects prevented full dosing of sorafenib and necessitated discontinuation of sorafenib in the majority of patients, yet antitumor efficacy seemed promising in combination with mTORi.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Benzenesulfonates / adverse effects*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary
  • Calcineurin Inhibitors
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary
  • Liver Transplantation
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Protein Kinase Inhibitors / adverse effects
  • Pyridines / adverse effects*
  • Recurrence
  • Retrospective Studies
  • Sorafenib
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzenesulfonates
  • Calcineurin Inhibitors
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Pyridines
  • Niacinamide
  • Sorafenib
  • TOR Serine-Threonine Kinases