title: High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation.
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.
authors.affiliation: Hepatobiliary and Transplant Surgery, University Medical Centre Hamburg -Eppendorf, Hamburg, Germany. katharina.staufer@meduniwien.ac.at
authors.forename: Katharina
authors.initials: K
authors.lastname: Staufer
authors.forename: Lutz
authors.initials: L
authors.lastname: Fischer
authors.forename: Barbara
authors.initials: B
authors.lastname: Seegers
authors.forename: Eik
authors.initials: E
authors.lastname: Vettorazzi
authors.forename: Bjoern
authors.initials: B
authors.lastname: Nashan
authors.forename: Martina
authors.initials: M
authors.lastname: Sterneck
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001557:Benzenesulfonates / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D065095:Calcineurin Inhibitors; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D016031:Liver Transplantation; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D011725:Pyridines / Q000009:adverse effects*; D012008:Recurrence; D012189:Retrospective Studies; D000077157:Sorafenib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D065095:Calcineurin Inhibitors; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D058570:TOR Serine-Threonine Kinases