title: Phase I adjuvant trial of sorafenib in patients with hepatocellular carcinoma after orthotopic liver transplantation.
abstract: BACKGROUND
  Post-transplant hepatocellular carcinoma recurrence has been reported to be between 15-18% and is higher among patients with high-risk features (bilobar tumor, macrovascular invasion, or multifocality). There are no known treatments which reduce risk of recurrence post-transplant. Sorafenib is currently approved for the treatment of advanced hepatocellular carcinoma. The objective of this phase I trial was to establish the safety and toxicity profile of sorafenib in high-risk patients with hepatocellular carcinoma who have undergone orthotopic liver transplantation.
  
  
  METHODS
  Patients with hepatocellular carcinoma on explant with above high risk features were eligible to start the study drug between 28 and 60 days after liver transplantation. Sorafenib was administered and escalated twice daily on three cohort dose levels: i) 400 mg/day, ii) 600 mg/day and iii) 800 mg/day.
  
  
  RESULTS
  Four patients newly transplanted were enrolled and received standard post-transplant medications. Dose-limiting toxicity was reached at the first cohort dose, with three out of four patients experiencing grade 3 toxicities. One patient experienced emerging grade 3 hand foot skin reaction leading to discontinuation of the study drug. Duration of sorafenib in the four patients was 0.7 months, 1.6 months, 3.5 months and 1.6 months, respectively.
  
  
  CONCLUSIONS
  Although a small number of patients were studied, toxicity seen at 400 mg/day is consistent with toxicity reported by a small parallel study by Siegel AB.
authors.affiliation: Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Tsinghua University Health System, Beijing, PRC.
authors.forename: Ning
authors.initials: N
authors.lastname: Jia
authors.forename: Iris
authors.initials: I
authors.lastname: Liou
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Halldorson
authors.forename: Robert
authors.initials: R
authors.lastname: Carithers
authors.forename: James
authors.initials: J
authors.lastname: Perkins
authors.forename: Jorge
authors.initials: J
authors.lastname: Reyes
authors.forename: Matthew
authors.initials: M
authors.lastname: Yeh
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stohr
authors.forename: Sujata
authors.initials: S
authors.lastname: Rao
authors.forename: Edward H
authors.initials: EH
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Phase I; adjuvant therapy; hepatocellular carcinoma; orthotopic liver transplantation; sorafenib