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      Combination of Sorafenib and Transarterial Chemoembolization in Selected Patients with Advanced-Stage Hepatocellular Carcinoma: A Retrospective Cohort Study at Three German Liver Centers

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          Transarterial chemoembolization (TACE) is the treatment of choice for patients with liver cancer without distant metastases or tumor growth into blood vessels. For the latter patients, sorafenib is a well-established oral medication. Combination of both treatments might also enhance effectiveness and survival in patients with advanced tumor stages. We retrospectively compared patients with advanced liver cancer (with distant metastases and/or tumor growth into blood vessels) from three German university hospitals who received either TACE alone, sorafenib alone or the combination treatment. We found that survival was prolonged for patients receiving the combination treatment without increasing frequency or severity of side effects. These results are in line with published results from Asian patients and show that this treatment might also be feasible in a Western population for selected patients with advanced liver cancer.

          Abstract

          Background and Aims. Systemic treatment with sorafenib has been the standard of care (SOC) in patients with advanced Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) for more than a decade. TACE has been reported to allow better local tumor control in selected patients with BCLC stage C HCC. Methods. A retrospective analysis of patients with BCLC stage C HCC that were treated with sorafenib and TACE was conducted; they were compared to BCLC stage C patients treated either with TACE or sorafenib in the same period of time outside a clinical trial. Results. A total of 201 patients with BCLC stage C were identified, who were treated with either sorafenib and TACE (group A; n = 54), sorafenib (group B; n = 82) or TACE (group C; n = 65). No significant difference in baseline characteristics was observed. Time to progression was 7.0 months (95% CI: 4.3–9.7), 4.1 months (95% CI: 3.6–4.7) and 5.0 months (95% CI: 2.9–7.1) in groups A, B and C, respectively, and overall survival was 16.5 months (95% CI: 15.0–18.1), 8.4 months (95% CI: 6.0–10.8) and 10.5 months (95% CI: 7.5–13.6), respectively (group A vs. group B: p < 0.001; group A vs. group C: p = 0.0023). Adverse events of grade 3/4 occurred in 34% of patients in group A. Conclusions. Although sorafenib is a SOC in patients with BCLC stage C HCC, TACE is frequently used as an additional locoregional treatment in selected patients. This combined approach resulted in a significant overall survival benefit in selected patients, although randomized trials have not yet proven this benefit.

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          Most cited references30

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          EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma

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            Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma

            The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma.
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              Sorafenib in advanced hepatocellular carcinoma.

              No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo. (ClinicalTrials.gov number, NCT00105443.) 2008 Massachusetts Medical Society
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                28 April 2021
                May 2021
                : 13
                : 9
                : 2121
                Affiliations
                [1 ]Department of Medicine 1, University Hospital Frankfurt, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany; christine.koch@ 123456kgu.de (C.K.); markus.goeller@ 123456uk-erlangen.de (M.G.); oliver.waidmann@ 123456kgu.de (O.W.); zeuzem@ 123456em.uni-frankfurt.de (S.Z.)
                [2 ]University Cancer Centre, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany
                [3 ]Department of Gastroenterology, Hepatology and Diabetology, Internal Medicine II, HELIOS Hospital Emil von Behring, 14165 Berlin, Germany; eckart.schott@ 123456helios-gesundheit.de
                [4 ]Department of Medicine II, University Hospital, Ludwig Maximilians University, 81377 Munich, Germany; Mark.op.den.Winkel@ 123456med.uni-muenchen.de (M.o.d.W.); philipp.paprottka@ 123456mri.tum.de (P.P.); frank.kolligs@ 123456helios-gesundheit.de (F.T.K.)
                [5 ]Department of Interventional Radiology, Klinikum rechts der Isar, Technical University Munich, 80333 Munich, Germany
                [6 ]Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany; stephan.zangos@ 123456af-k.de (S.Z.); thomas.vogl@ 123456kgu.de (T.V.)
                [7 ]Department of Radiology and Nuclear Medicine, Klinik am Eichert und Helfenstein Klinik, 73312 Göppingen, Germany
                [8 ]Department of General and Viszeral Surgery, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany; wolf.bechstein@ 123456kgu.de
                [9 ]Department of Internal Medicine and Gastroenterology, Helios-Klinikum Berlin-Buch, 13125 Berlin, Germany
                Author notes
                [* ]Correspondence: trojan@ 123456em.uni-frankfurt.de ; Tel.: +49-69-6301-7860; Fax: +49-69-6301-83776
                Author information
                https://orcid.org/0000-0002-4143-5188
                https://orcid.org/0000-0002-3267-8145
                Article
                cancers-13-02121
                10.3390/cancers13092121
                8124282
                33924810
                dfcaeaf5-f8e7-4839-bcc2-a1d5d2425bd5
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 10 March 2021
                : 26 April 2021
                Categories
                Article

                hcc,tace,sorafenib,treatment
                hcc, tace, sorafenib, treatment

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