Safe use of sorafenib in a patient undergoing salvage liver transplantation for recurrent hepatocellular carcinoma after hepatic resection

Kim, Richard; Menon, Narayanan; Aucejo, Federico

doi:10.1007/s12032-010-9625-x

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…However, the overall experience with Sorafenib in HCC patients awaiting LT is actually even bleaker. Concerns regarding the potential negative side effects of Sorafenib have been raised [ 17 , 18 , 38 - 40 ]. Nevertheless, the performance of the trial was encouraged by emerging reports about a near absence of liver toxicity or treatment-related deaths [ 12 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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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 registration ISRCTN24081794

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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…In this cohort of liver transplant recipients side effects prevented full dosing of sorafenib and necessitated discontinuation of sorafenib in the majority of patients, yet antitumor efficacy seemed promising in combination with mTORi. are yet only anecdotal [13][14][15][16][17][18]. Enhanced anticancer properties in vitro and in vivo were suggested when sorafenib was combined with mTORi [16,19,20].…”

Section: Introductionmentioning

confidence: 99%

High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation

Staufer

Fischer

Seegers

et al. 2012

Transplant International

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Summary Treatment options of recurrent hepatocellular carcinoma (HCC) after liver transplantation are limited and data on systemic compounds for advanced tumor stages in transplant recipients are sparse. We retrospectively analyzed the toxicity, tolerability, and efficacy of sorafenib in combination with mTOR inhibitors (mTORi), or calcineurin inhibitors (CNI) in transplant recipients with recurrent HCC. In total, 20 of 92 patients transplanted for HCC within a 10‐year time period, experienced tumor recurrence. In case of ineligibility for other treatment options, patients received sorafenib (n = 13). In addition, CNI were stopped and switched to mTORi in nine patients, whereas CNI were continued in four patients. Grade 3–4 adverse events were observed in 92% of all patients necessitating sorafenib discontinuation in 77%. The most common severe adverse events were acute hepatitis, diarrhea, hand‐foot – skin reaction and bone marrow suppression. In patients receiving sorafenib/mTORi one patient achieved partial response, and four achieved stable disease. In this cohort of liver transplant recipients side effects prevented full dosing of sorafenib and necessitated discontinuation of sorafenib in the majority of patients, yet antitumor efficacy seemed promising in combination with mTORi.

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“…The use of potent VEGF inhibitors are not without concern due to their effect on angiogenesis and wound healing 42, 43. Limited experiences with preoperative use of Sorafenib in renal cell carcinomas have been published 44, while the literature in surgical HCC candidates is limited 45. Clinical trials in surgical HCC patients have been suggested 46.…”

Section: Discussionmentioning

confidence: 99%

RAF‐targeted therapy for hepatocellular carcinoma in the regenerating liver

Shi

Liu

Wierød

et al. 2012

Journal of Surgical Oncology

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Safe use of sorafenib in a patient undergoing salvage liver transplantation for recurrent hepatocellular carcinoma after hepatic resection

Cited by 11 publications

References 10 publications

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

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

High toxicity of sorafenib for recurrent hepatocellular carcinoma after liver transplantation

RAF‐targeted therapy for hepatocellular carcinoma in the regenerating liver

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