Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation

Authors

  • Carlos Gomez-Martin,

    Corresponding author
    1. Gastrointestinal Cancer Unit, October 12 University Hospital, Madrid, Spain
    • Gastrointestinal Cancer Clinical Research Unit, Clinical Research Program, Spanish National Cancer Research Center, Fuenlabrada University Hospital, Camino del Molino 2, Fuenlabrada, Madrid, Spain 28942
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    • Telephone: 91 732 8000; FAX: 91 224 6980

  • Javier Bustamante,

    1. Hepatology and Liver Transplant Unit, Cruces University Hospital, Bilbao, Spain
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  • Javier F. Castroagudin,

    1. Hepatology and Liver Transplant Unit, Santiago University Hospital Complex, Santiago de Compostela, Spain
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  • Magdalena Salcedo,

    1. Hepatology and Liver Transplant Unit, Gregorio Marañon University Hospital/Network Center for Biomedical Research in Hepatic and Digestive Diseases, Madrid, Spain
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  • Elena Garralda,

    1. Gastrointestinal Cancer Unit, October 12 University Hospital, Madrid, Spain
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  • Milagros Testillano,

    1. Hepatology and Liver Transplant Unit, Cruces University Hospital, Bilbao, Spain
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  • Ignacio Herrero,

    1. Hepatology Unit/Network Center for Biomedical Research in Hepatic and Digestive Diseases, University Clinic of Navarra, Pamplona, Spain
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  • Ana Matilla,

    1. Hepatology and Liver Transplant Unit, Gregorio Marañon University Hospital/Network Center for Biomedical Research in Hepatic and Digestive Diseases, Madrid, Spain
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  • Bruno Sangro

    1. Hepatology Unit/Network Center for Biomedical Research in Hepatic and Digestive Diseases, University Clinic of Navarra, Pamplona, Spain
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Abstract

There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation. This open, multicenter, retrospective, uncontrolled cohort study was designed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin (mTOR) inhibitor and sorafenib in this setting. In 31 patients who suffered from HCC recurrence after liver transplantation, the immunosuppressive therapy was changed to mTOR inhibitors, and systemic treatment with sorafenib was initiated. This combination was maintained until symptomatic tumor progression, death, hepatic decompensation, or unacceptable toxicity occurred. Primary treatment efficacy was determined by overall survival and progression-free survival, and secondary efficacy was determined by the overall response rate. Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed. The overall response rate according to the Response Evaluation Criteria in Solid Tumors was 3.8% (1/26), and there was sustained stabilization of the disease in 13 additional cases (50.0%). The median overall survival was 19.3 months [95% confidence interval (CI) = 13.4–25.1 months], and the median time to progression was 6.77 months (95% CI = 2.3–11.1 months). Only 2 grade 3/4 cases of hyperglycemia and 1 case of grade 3/4 mucositis were reported, and they were possibly related to mTOR inhibitors. The most common severe adverse event probably related to sorafenib was diarrhea (12.9%). In conclusion, the coadministration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with post–liver transplant HCC recurrence not suitable for radical therapy. The toxicity and efficacy need to be further evaluated in randomized controlled studies for this combination to be considered a valid option. Liver Transpl 18:45–52, 2012. © 2011 AASLD.

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