Adverse events affect sorafenib efficacy in patients with recurrent hepatocellular carcinoma after liver transplantation: experience at a single center and review of the literature

Eur J Gastroenterol Hepatol. 2013 Feb;25(2):180-6. doi: 10.1097/MEG.0b013e328359e550.

Abstract

Aims: The aim of this study was to assess the safety and efficacy of sorafenib, with or without everolimus, in the treatment of recurrent hepatocellular carcinoma (HCC) after an orthotopic liver transplantation (OLT).

Methods: We reviewed the outcome of our consecutive cohort series of patients. Eleven patients (nine men) with recurrent HCC after OLT were treated. Four patients received cyclosporine plus sorafenib at a starting dose of 400 mg twice daily; seven received the combination of sorafenib (same dosage) and everolimus. Sorafenib was reduced or stopped according to the drug label.

Results: The median time to recurrence was 12 months (range 2-66). The mean age at the start of treatment was 57 ± 9 years. Sorafenib was withdrawn because of intolerance or side-effects in four (36%) patients. Dose reduction because of adverse events or intolerance was required in 91% of patients after 26 ± 11 days from the start of treatment. The average length of treatment was 68 days (range 15-444). One patient died because of a massive gastrointestinal bleeding while receiving sorafenib and everolimus. The most frequent adverse events were fatigue (54%), skin toxicity (45%), and hypophosphatemia (36%). Two patients (18%) showed a radiological partial response, one (9%) had a stable disease, and six (54%) showed a progressive disease. None of the patients achieved a complete response. Treatment response could not be assessed in two (18%) patients. The overall median survival since the start of treatment was 5 months. One-year survival was 18%.

Conclusion: Sorafenib, with or without mammalian target of rapamycin inhibitors, is poorly tolerated and rarely effective in the treatment of recurrent HCC after OLT.

Publication types

  • Review

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / secondary
  • Carcinoma, Hepatocellular / surgery
  • Drug Evaluation
  • Everolimus
  • Female
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / surgery
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives
  • Sorafenib
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Everolimus
  • Sorafenib
  • Sirolimus