Phase I adjuvant trial of sorafenib in patients with hepatocellular carcinoma after orthotopic liver transplantation.

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. 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. 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. 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.