Phase i trial of sorafenib following liver transplantation in patients with high-risk hepatocellular carcinoma

Abby B. Siegel, Anthony B. El-Khoueiry, Richard S. Finn, Katherine A. Guthrie, Abhishek Goyal, Alan P. Venook, Charles D. Blanke, Elizabeth C. Verna, Lorna Dove, Jean Emond, Tomoaki Kato, Benjamin Samstein, Ronald Busuttil, Helen Remotti, Amy Coffey, Robert S. Brown

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Liver transplantation offers excellent long-term survival for hepatocellular carcinoma (HCC) patients who fall within established criteria. For those outside such criteria, or with high-risk pathologic features in the explant, HCC recurrence rates are higher. We conducted a multicenter phase I trial of sorafenib in liver transplantation patients with high-risk HCC. Subjects had HCC outside the Milan criteria (pre- or post-transplant), poorly differentiated tumors, or vascular invasion. We used a standard 3+3 phase I design with a planned duration of treatment of 24 weeks. Correlative studies included the number of circulating endothelial cells (CECs), plasma biomarkers, and tumor expression of p-Erk, p-Akt, and c-Met in tissue micro-arrays. We enrolled 14 patients with a median age of 63 years. Of these, 93% were men and 71% had underlying hepatitis C virus (HCV) and 21% had HBV. The maximum tolerated dose of sorafenib was 200 mg BID. Grade 3-4 toxicities seen in >10% of subjects included leukopenia (21%), elevated gamma-glutamyl transferase (21%), hypertension (14%), hand-foot syndrome (14%) and diarrhea (14%). Over a median follow-up of 953 days, one patient died and four recurred. The mean CEC number at baseline was 21 cells/4 ml for those who recurred, and 80 cells/4 ml for those who did not (p=0.10). Mean soluble vascular endothelial growth factor receptor-2 levels decreased after 1 month on sorafenib (p=0.09), but did not correlate with recurrence. There was a trend for tumor c-Met expression to correlate with increased risk of recurrence. Post-transplant sorafenib was found to be feasible and tolerable at 200 mg PO BID. The effect of post-transplant sorafenib on recurrence-free survival is potentially promising but needs further validation in a larger study.

Original languageEnglish (US)
Pages (from-to)115-125
Number of pages11
JournalLiver Cancer
Issue number2
StatePublished - Apr 27 2015


  • Hepatocellular carcinoma
  • High risk
  • Liver transplant
  • Phase I
  • Sorafenib

ASJC Scopus subject areas

  • Hepatology
  • Oncology


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