A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Andreas A. Schnitzbauer, Carl Zuelke, Christian Graeb, Justine Rochon, Itxarone Bilbao, Patrizia Burra, Koert P. de Jong, Christophe Duvoux, Norman M. Kneteman, Rene Adam, Wolf O. Bechstein, Thomas Becker, Susanne Beckebaum, Olivier Chazouillères, Umberto Cillo, Michele Colledan, Fred Fändrich, Jean Gugenheim, Johann P. Hauss, Michael HeiseErnest Hidalgo, Neville Jamieson, Alfred Königsrainer, Philipp E. Lamby, Jan P. Lerut, Heikki Mäkisalo, Raimund Margreiter, Vincenzo Mazzaferro, Ingrid Mutzbauer, Gerd Otto, Georges Philippe Pageaux, Antonio D. Pinna, Jacques Pirenne, Magnus Rizell, Giorgio Rossi, Lionel Rostaing, Andre Roy, Victor S. Turrion, Jan Schmidt, Roberto I. Troisi, Bart van Hoek, Umberto Valente, Philippe Wolf, Heiner Wolters, Darius F. Mirza, Tim Scholz, Rudolf Steininger, Gunnar Soderdahl, Simone I. Strasser, Karl Walter Jauch, Peter Neuhaus, Hans J. Schlitt, Edward K. Geissler

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.

Original languageEnglish
Article number190
JournalBMC Cancer
Volume10
DOIs
Publication statusPublished - May 11 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

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