Immunosuppression in Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

Summary

The purpose of this study is to determine the safety and efficacy of sirolimus-based immunosuppressive therapy in patients following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), with regard to HCC recurrence-free patient survival.

Timeline

Start

2006-01

Primary completion

2009-04

Completion

2014-05

Outcome

Missed primary endpoint

paper Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met PMID 32889867 ↗

Publications

• Schnitzbauer AA, Filmann N, Adam R, Bachellier P, Bechstein WO, Becker T, Bhoori S, Bilbao I, Brockmann J, Burra P, Chazoullieres O, Cillo U, Colledan M, Duvoux C, Ganten TM, Gugenheim J, Heise M, van Hoek B, Jamieson N, de Jong KP, Klein CG, Klempnauer J, Kneteman N, Lerut J, Makisalo H, Mazzaferro V, Mirza DF, Nadalin S, Neuhaus P, Pageaux GP, Pinna AD, Pirenne J, Pratschke J, Powel J, Rentsch M, Rizell M, Rossi G, Rostaing L, Roy A, Scholz T, Settmacher U, Soliman T, Strasser S, Soderdahl G, Troisi RI, Turrion VS, Schlitt HJ, Geissler EK. mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors. Ann Surg. 2020 Nov;272(5):855-862. doi: 10.1097/SLA.0000000000004280.
• Geissler EK, Schnitzbauer AA, Zulke C, Lamby PE, Proneth A, Duvoux C, Burra P, Jauch KW, Rentsch M, Ganten TM, Schmidt J, Settmacher U, Heise M, Rossi G, Cillo U, Kneteman N, Adam R, van Hoek B, Bachellier P, Wolf P, Rostaing L, Bechstein WO, Rizell M, Powell J, Hidalgo E, Gugenheim J, Wolters H, Brockmann J, Roy A, Mutzbauer I, Schlitt A, Beckebaum S, Graeb C, Nadalin S, Valente U, Turrion VS, Jamieson N, Scholz T, Colledan M, Fandrich F, Becker T, Soderdahl G, Chazouilleres O, Makisalo H, Pageaux GP, Steininger R, Soliman T, de Jong KP, Pirenne J, Margreiter R, Pratschke J, Pinna AD, Hauss J, Schreiber S, Strasser S, Klempnauer J, Troisi RI, Bhoori S, Lerut J, Bilbao I, Klein CG, Konigsrainer A, Mirza DF, Otto G, Mazzaferro V, Neuhaus P, Schlitt HJ. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Transplantation. 2016 Jan;100(1):116-25. doi: 10.1097/TP.0000000000000965.
• Schnitzbauer AA, Zuelke C, Graeb C, Rochon J, Bilbao I, Burra P, de Jong KP, Duvoux C, Kneteman NM, Adam R, Bechstein WO, Becker T, Beckebaum S, Chazouilleres O, Cillo U, Colledan M, Fandrich F, Gugenheim J, Hauss JP, Heise M, Hidalgo E, Jamieson N, Konigsrainer A, Lamby PE, Lerut JP, Makisalo H, Margreiter R, Mazzaferro V, Mutzbauer I, Otto G, Pageaux GP, Pinna AD, Pirenne J, Rizell M, Rossi G, Rostaing L, Roy A, Turrion VS, Schmidt J, Troisi RI, van Hoek B, Valente U, Wolf P, Wolters H, Mirza DF, Scholz T, Steininger R, Soderdahl G, Strasser SI, Jauch KW, Neuhaus P, Schlitt HJ, Geissler EK. A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma. BMC Cancer. 2010 May 11;10:190. doi: 10.1186/1471-2407-10-190.
• Geissler EK. Rapamycin enhances lifespan: at last, an advantage for transplant recipients? Nephrol Dial Transplant. 2009 Dec;24(12):3623-5. doi: 10.1093/ndt/gfp496. Epub 2009 Sep 22. No abstract available.
• Treiber G. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther. 2009 Feb;9(2):247-61. doi: 10.1586/14737140.9.2.247.

Drugs

Indications