TY  - JOUR
A1  - Schnitzbauer, Andreas
A1  - Zuelke, Carl
A1  - Graeb, Christian
A1  - Rochon, Justine
A1  - Bilbao, Itxarone
A1  - Burra, Patrizia
A1  - de Jong, Koert P.
A1  - Duvoux, Christophe
A1  - Kneteman, Norman M.
A1  - Adam, Rene
A1  - Bechstein, Wolf Otto
A1  - Becker, Thomas
A1  - Beckebaum, Susanne
A1  - Chazouilleres, Olivier
A1  - Cillo, Umberto
A1  - Colledan, Michele
A1  - Fandrich, Fred
A1  - Gugenheim, Jean
A1  - Hauss, Johann P.
A1  - Heise, Michael
A1  - Hidalgo, Ernest
A1  - Jamieson, Neville
A1  - Königsrainer, Alfred
A1  - Lamby, Philipp E.
A1  - Lerut, Jan P.
A1  - Makisalo, Heikki
A1  - Margreiter, Raimund
A1  - Mazzaferro, Vincenzo
A1  - Mutzbauer, Ingrid
A1  - Otto, Gerd
A1  - Pageaux, Georges-Philippe
A1  - Pinna, Antonio D.
A1  - Pirenne, Jacques
A1  - Rizell, Magnus
A1  - Rossi, Giorgio
A1  - Rostaing, Lionel
A1  - Roy, Andre
A1  - Turrion, Victor Sanchez
A1  - Schmidt, Jan
A1  - Troisi, Roberto I.
A1  - Hoek, Bart van
A1  - Valente, Umberto
A1  - Wolf, Philippe
A1  - Wolters, Heiner
A1  - Mirza, Darius F.
A1  - Scholz, Tim
A1  - Steininger, Rudolf
A1  - Soderdahl, Gunnar
A1  - Strasser, Simone I.
A1  - Jauch, Karl-Walter
A1  - Neuhaus, Peter
A1  - Schlitt, Hans J.
A1  - Geissler, Edward K.
T1  - A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma
T2  - BMC Cancer
N2  - 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: 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 3-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. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7871
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-77290
N1  - © 2010 Schnitzbauer et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 10
IS  - 190
ER  -