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




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BMC Cancer

, 15:392

Clinical oncology

Abstract

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

KeywordsHepatocellular carcinoma Liver transplantation Sorafenib Transarterial chemoembolization AbbreviationsCIFCumulative Incidence Functions

CRComplete Response

CTCAECommon Terminology Criteria for Adverse Events

DCRDisease Control Rate

EASLDEuropean Association for the Study of Liver Disease

HCCHepatocellular Carcinoma

IITInvestigator-initiated Trial

LTLiver Transplantation

mRECISTModified Response Evaluation Criteria in Solid Tumours

ORRObjective Response Rate

PFSProgression-free Survival

PRPartial Response

SDStable Disease

TACETransarterial chemoembolization

TTPTime-to-Progression

TTLTTime-to-Liver-Transplantation

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Fuente: https://link.springer.com/







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