Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective, randomized, double-blind, phase III trial

BMC Cancer

Research Article

Otto Kollmar¹  Markus W Büchler²  Katrin Hoffmann²  Peter Schemmer³  Utz Settmacher⁴  Daniel Gotthardtp⁵  Tom Ganten⁵  Boris Radeleff⁶  Silvio Nadalin⁷  Dirk Jäger⁸  Christof von Kalle⁸  Irini Karapanagiotou-Schenkel⁸ 

[1] Department of General and Visceral Surgery, Georg-August-University, Robert-Koch-Str. 40, 37075, Göttingen, Germany;Department of General-, Visceral- and Transplantation-Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany;Department of General-, Visceral- and Transplantation-Surgery, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany;Department of General- Visceral- and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany;Department of General-, Visceral- and Vascular-Surgery, University Hospital, Erlanger Allee 101, 07747, Jena, Germany;Department of Internal Medicine, Ruprecht-Karls-University, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany;Department of Radiology, Ruprecht-Karls-University, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany;Department of Surgery, University Hospital, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany;National Centre of Tumour Diseases, Ruprecht-Karls-University, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany;

关键词: Hepatocellular carcinoma;    Liver transplantation;    Sorafenib;    Transarterial chemoembolization;   

DOI  :  10.1186/s12885-015-1373-z

 received in 2014-08-30, accepted in 2015-04-27,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundLiver Transplantation (LT) is treatment of choice for patients with hepatocellular carcinoma (HCC) within MILAN Criteria. Tumour progression and subsequent dropout from waiting list have significant impact on the survival. Transarterial chemoembolization (TACE) controls tumour growth in the treated HCC nodule, however, the risk of tumour development in the untreated liver is increased by simultaneous release of neo-angiogenic factors. Due to its anti-angiogenic effects, Sorafenib delays the progression of HCC. Aim of this study was to determine whether combination of TACE and Sorafenib improves tumour control in HCC patients on waiting list for LT.MethodsFifty patients were randomly assigned on a 1:1 ratio in double-blinded fashion at four centers in Germany and treated with TACE plus either Sorafenib (n = 24) or placebo (n = 26). The end of treatment was development of progressive disease according to mRECIST criteria or LT. The primary endpoint of the trial was the Time-to-Progression (TTP). Other efficacy endpoints were Tumour Response, Progression-free Survival (PFS), and Time-to-LT (TTLT).ResultsThe median time of treatment was 125 days with Sorafenib and 171 days with the placebo. Fourteen patients (seven from each group) developed tumour progression during the course of the study period. The Hazard Ratio of TTP was 1.106 (95% CI: 0.387, 3.162). The results of the Objective Response Rate, Disease Control Rate, PFS, and TTLT were comparable in both groups. The incidence of AEs was comparable in the placebo group (n = 23, 92%) and in the Sorafenib group (n = 23, 96%). Twelve patients (50%) on Sorafenib and four patients (16%) on placebo experienced severe treatment-related AEs.ConclusionThe TTP is similar after neo-adjuvant treatment with TACE and Sorafenib before LT compared to TACE and placebo. The Tumour Response, PFS, and TTLT were comparable. The safety profile of the Sorafenib group was similar to that of the placebo group.Trial registrationISRCTN24081794

【 授权许可】

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© Hoffmann et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.