Latest documents http://publikationen.ub.uni-frankfurt.de/index/index/ Fri, 08 Oct 2010 14:49:50 +0200 Fri, 08 Oct 2010 14:49:50 +0200 http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7871 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) 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 Otto Bechstein; Thomas Becker; Susanne Beckebaum; Olivier Chazouilleres; Umberto Cillo; Michele Colledan; Fred Fandrich; Jean Gugenheim; Johann P. Hauss; Michael Heise; Ernest Hidalgo; Neville Jamieson; Alfred Konigsrainer; Philipp E. Lamby; Jan P. Lerut; Heikki Makisalo; 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 Sanchez 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 article http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7871 Tue, 10 Aug 2010 14:49:50 +0200