eprintid: 19429
rev_number: 20
eprint_status: archive
userid: 1589
dir: disk0/00/01/94/29
datestamp: 2016-01-08 13:25:26
lastmod: 2024-03-26 06:38:21
status_changed: 2016-01-08 13:25:26
type: article
metadata_visibility: show
creators_name: Hoffmann, Katrin
creators_name: Ganten, Tom
creators_name: Gotthardt, Daniel
creators_name: Radeleff, Boris
creators_name: Settmacher, Utz
creators_name: Kollmar, Otto
creators_name: Nadalin, Silvio
creators_name: Karapanagiotou-Schenkel, Irini
creators_name: von Kalle, Christof
creators_name: Jäger, Dirk
creators_name: Büchler, Markus W.
creators_name: Schemmer, Peter
title: Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective, randomized, double-blind, phase III trial
subjects: 610
divisions: 910100
divisions: 910200
divisions: 911400
abstract: Background: Liver 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.   Methods: Fifty 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).   Results: The 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.   Conclusion: The 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 registration:   ISRCTN24081794     
date: 2015
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1656777460
own_urn: urn:nbn:de:bsz:16-heidok-194296
language: eng
bibsort: HOFFMANNKAIMPACTOFNE2015
full_text_status: public
publication: BMC Cancer
volume: 15
number: 392
place_of_pub: London
pagerange: 1-11
issn: 1471-2407
citation:   Hoffmann, Katrin ; Ganten, Tom ; Gotthardt, Daniel ; Radeleff, Boris ; Settmacher, Utz ; Kollmar, Otto ; Nadalin, Silvio ; Karapanagiotou-Schenkel, Irini ; von Kalle, Christof ; Jäger, Dirk ; Büchler, Markus W. ; Schemmer, Peter  (2015) Impact of neo-adjuvant Sorafenib treatment on liver transplantation in HCC patients - a prospective, randomized, double-blind, phase III trial.  BMC Cancer, 15 (392).  pp. 1-11.  ISSN 1471-2407     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19429/1/12885_2015_Article_1373.pdf