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

被引：125

作者：

Schnitzbauer, Andreas A. ^{[1
]}

Zuelke, Carl ^{[1
]}

Graeb, Christian ^{[2
]}

Rochon, Justine ^{[3
]}

Bilbao, Itxarone ^{[4
]}

Burra, Patrizia ^{[5
]}

de Jong, Koert P. ^{[6
]}

Duvoux, Christophe ^{[7
]}

Kneteman, Norman M. ^{[8
]}

Adam, Rene ^{[9
,10
]}

Bechstein, Wolf O. ^{[11
]}

Becker, Thomas ^{[12
]}

Beckebaum, Susanne ^{[13
,14
,15
,16
]}

Chazouilleres, Olivier ^{[17
,18
]}

Cillo, Umberto ^{[19
]}

Colledan, Michele ^{[20
]}

Faendrich, Fred ^{[21
]}

Gugenheim, Jean ^{[22
]}

Hauss, Johann P. ^{[23
]}

Heise, Michael ^{[24
]}

Hidalgo, Ernest ^{[25
]}

Jamieson, Neville ^{[26
]}

Koenigsrainer, Alfred ^{[27
]}

Lamby, Philipp E. ^{[1
]}

Lerut, Jan P. ^{[28
]}

Makisalo, Heikki ^{[29
]}

Margreiter, Raimund ^{[30
]}

Mazzaferro, Vincenzo ^{[31
]}

Mutzbauer, Ingrid ^{[1
]}

Otto, Gerd ^{[32
]}

Pageaux, Georges-Philippe ^{[33
]}

Pinna, Antonio D. ^{[34
]}

Pirenne, Jacques ^{[35
]}

Rizell, Magnus ^{[36
]}

Rossi, Giorgio ^{[37
]}

Rostaing, Lionel ^{[38
]}

Roy, Andre ^{[39
]}

Sanchez Turrion, Victor ^{[40
]}

Schmidt, Jan ^{[41
]}

Troisi, Roberto I. ^{[42
]}

van Hoek, Bart ^{[43
]}

Valente, Umberto ^{[44
]}

Wolf, Philippe ^{[45
]}

Wolters, Heiner ^{[46
]}

Mirza, Darius F. ^{[47
]}

Scholz, Tim ^{[48
]}

Steininger, Rudolf ^{[49
]}

Soderdahl, Gunnar ^{[50
]}

Strasser, Simone I. ^{[51
]}

Jauch, Karl-Walter ^{[2
]}

机构：

[1] Univ Hosp Regensburg, Dept Surg, Regensburg, Germany

[2] Univ Munich, Dept Surg, Munich, Germany

[3] Regensburg Univ Hosp, Ctr Clin Studies, Regensburg, Germany

[4] Hosp Univ Vall Hebron, Dept Hepatobiliopancreat Surg & Transplant, Barcelona, Spain

[5] Univ Hosp Padua, Dept Surg & Gastroenterol Sci, Gastroenterol Sect, Padua, Italy

[6] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Div Hepatopancreaticobiliary Surg & Liver Transpl, Groningen, Netherlands

[7] Univ Paris 12, Hop Henri Mondor, AP HP, Serv Hepatogastroenterol,Unite Transplantat Hepat, F-94010 Creteil, France

[8] Univ Alberta, Sect Hepatobiliary Pancreat & Transplant Surg, Edmonton, AB, Canada

[9] Hop Paul Brousse, AP HP, Ctr Hepatobiliaire, Villejuif, France

[10] Univ Paris 11, UMR S776, F-94800 Villejuif, France

[11] Goethe Univ Frankfurt, Dept Gen & Vasc Surg, Frankfurt, Germany

[12] Hannover Med Sch, Clin Gen Visceral & Transplant Surg, D-30623 Hannover, Germany

[13] Univ Duisburg Essen, Univ Hosp Essen, Dept Gastroenterol, Duisburg, Germany

[14] Univ Duisburg Essen, Univ Hosp Essen, Dept Gen Visceral & Transplantat Surg, Duisburg, Germany

[15] Univ Duisburg Essen, Univ Hosp Essen, Dept Gen Visceral & Transplantat Surg, Essen, Germany

[16] Univ Duisburg Essen, Univ Hosp Essen, Dept Gastroenterol, Essen, Germany

[17] Univ Paris 06, Hop St Antoine, Serv Hepatol, Paris, France

[18] Univ Paris 06, Hop St Antoine, Ctr Reference Malad Inflammatoires Foie & Voies B, Paris, France

[19] Azienda Osped Padova, Dipartimento Chirurg Gen & Trapianti Organo, Unita Chirurg Epatobiliare & Trapianto Epat, Padua, Italy

[20] Osped Riuniti Bergamo, Azienda Osped, Liver & Lung Transplantat Unit, I-24100 Bergamo, Italy

[21] Univ Hosp Schleswig Holstein, Dept Gen & Cardiothorac Surg, Kiel, Germany

[22] Hop Archet, Serv Chirurg Digest & Transplantat Hepat, Nice, France

[23] Univ Leipzig, Clin Visceral Transplantat Thorac & Vasc Surg, Leipzig, Germany

[24] Univ Jena, Univ Hosp, Dept Gen Visceral & Vasc Surg, Jena, Germany

[25] Royal Infirm Edinburgh NHS Trust, Scottish Liver Transplant Unit, Edinburgh EH16 4SA, Midlothian, Scotland

[26] Addenbrookes Hosp, Dept Surg, Cambridge CB2 2QQ, England

[27] Univ Tubingen Hosp, Dept Gen Visceral & Transplantat Surg, Tubingen, Germany

[28] Catholic Univ Louvain, Dept Abdominal & Transplantat Surg, B-1200 Brussels, Belgium

[29] Helsinki Univ Hosp, Dept Transplantat & Liver Surg, Surg Clin, Helsinki, Finland

[30] Med Univ Innsbruck, Dept Gen & Transplant Surg, Innsbruck, Austria

[31] NCI, Milan, Italy

[32] Johannes Gutenberg Univ Mainz, Dept Transplantat & Hepatobiliarypancreat Surg, Mainz, Germany

[33] CHU St Eloi, Liver Transplant Unit, Montpellier, France

[34] St Orsola Malpighi Univ Hosp, Transplant Gen & Emergency Surg DPT, Bologna, Italy

[35] Univ Hosp Leuven, Louvain, Belgium

[36] Sahlgrens Univ Hosp, Dept Surg, Transplantat & Liver Surg Serv, Gothenburg, Sweden

[37] Fondaz IRCCS Osped Maggiore Policlin, Unita Operat Chirurg Gen & Trapianti Fegato, Milan, Italy

[38] CHU Rangueil, Univ Hosp, Nephrol Dialysis & Organ Transplant Unit, F-31054 Toulouse, France

[39] Hop St Luc, CHUM, Dept Surg, Montreal, PQ H2X 1P1, Canada

[40] Hosp Univ Puerta Hierro, Liver Transplant Unit, Madrid, Spain

[41] Heidelberg Univ, Dept Gen Surg, Heidelberg, Germany

[42] Ghent Univ Hosp, Sch Med, Liver Transplantat Serv, Dept Gen & Hepatobiliary Surg, B-9000 Ghent, Belgium

[43] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands

[44] San Martino Univ Hosp, Dept Transplantat, Genoa, Italy

[45] Hop Hautepierre, Ctr Chirurg Viscerale & Transplantat, Strasbourg, France

[46] Univ Munster, Dept Gen & Visceral Surg, Munster, Germany

[47] Queen Elizabeth Hosp, Hepatobiliary Pancreat Surg Unit, Birmingham B15 2TH, W Midlands, England

[48] Univ Hosp, Rikshosp, Transplant Sect, Dept Surg, Oslo, Norway

[49] Med Univ Vienna, Dept Surg, Div Transplantat, Vienna, Austria

[50] Karolinska Univ, Huddinge Hosp, Dept Transplantat Surg, Stockholm, Sweden

来源：

BMC CANCER | 2010年 / 10卷

关键词：

ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; TUMOR PROGRESSION; RAPAMYCIN; CANCER; CYCLOSPORINE; EFFICACY; THERAPY; TARGET; MODEL;

D O I：

10.1186/1471-2407-10-190

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 antineoplastic 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 2(1/2)-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.

引用

页数：8

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