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      The effect of apatinib in the treatment of sorafenib resistant metastatic hepatocellular carcinoma : A case report

      case-report
      , MD, , MD, , PhD, , MD
      Medicine
      Wolters Kluwer Health
      apatinib, drug resistance, hepatocellular carcinoma, sorafenib, targeted therapy

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          Abstract

          Rationale:

          Most patients with hepatocellular carcinoma (HCC) have lost the chance of radical treatment at the time of their visit, and the prognosis of metastatic HCC is even worse. Sorafenib is currently regarded as a first-line systemic therapy in patients with advanced and metastatic HCC. Apatinib is a new inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase, which has been reported to be effective in some solid tumors. We herein report a case of apatinib in the treatment of the patient with metastatic HCC who was resistant to sorafenib.

          Patient concerns:

          A 41-year-old Chinese man with a history of chronic hepatitis B had undergone an emergency partial hepatectomy for tumor ruptured. Despite the treatment with transcatheter arterial chemoembolization and sorafenib, the progression of tumor failed to control.

          Diagnoses:

          Although the patient had been treated with sorafenib (400 mg, twice daily) for 10 months, computed tomography documented radiological progression.

          Interventions:

          Due to disease progression, failure of sorafenib and positive expression of vascular endothelial growth factor (VEGF), the drug regimen was changed to apatinib 250 mg once daily. Due to some degree of resistance, the dose was increased up to 425 mg once daily.

          Outcomes:

          The patient had a disease-free progression of 7 months at 250 mg apatinib. The dosage was adjusted to 425 mg due to drug resistance and the side effects were tolerable. The patient has survived a total of 19 months under apatinib.

          Lessons:

          Apatinib may be a substitute for the HCC patients with sorafenib resistance in the future, especially for those with high expression of VEGF.

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          Most cited references8

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          YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo.

          Angiogenesis is an important process in cell development, especially in cancer. Vascular endothelial growth factor (VEGF) signaling is an important regulator of angiogenesis. Several therapies that act against VEGF signal transduction have been developed, including YN968D1, which is a potent inhibitor of the VEGF signaling pathway. This study investigated the antitumor activity of YN968D1 (apatinib mesylate) in vitro and in vivo. YN968D1 potently suppressed the kinase activities of VEGFR-2, c-kit and c-src, and inhibited cellular phosphorylation of VEGFR-2, c-kit and PDGFRβ. YN968D1 effectively inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells induced by FBS, and blocked the budding of rat aortic ring. In vivo, YN968D1 alone and in combination with chemotherapeutic agents effectively inhibited the growth of several established human tumor xenograft models with little toxicity. A phase I study of YN968D1 has shown encouraging antitumor activity and a manageable toxicity profile. These findings suggest that YN968D1 has promise as an antitumor drug and might have clinical benefits. © 2011 Japanese Cancer Association.
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            Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: A systematic review and meta-analysis

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              Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma

              Background A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC. Methods Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a “VEGF decrease.” An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter. Results Patients who had a VEGF decrease at week 8 (n = 14) had a longer median survival than those who did not have a VEGF decrease (n = 49; 30.9 months vs 14.4 months; P = .038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n = 6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival. Conclusions A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                December 2018
                10 December 2018
                : 97
                : 49
                : e13388
                Affiliations
                Department of Interventional Radiology, the First People's Hospital of Changzhou, 185# Juqian Street, Changzhou, Jiangsu Province, China.
                Author notes
                []Correspondence: Qi Wang, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China. (e-mail: czwangqi666@ 123456sina.com ).
                Article
                MD-D-18-04266 13388
                10.1097/MD.0000000000013388
                6310601
                30544412
                fef8337f-e44b-435f-b655-53e524d0485d
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 24 June 2018
                : 30 October 2018
                Categories
                4500
                Research Article
                Clinical Case Report
                Custom metadata
                TRUE

                apatinib,drug resistance,hepatocellular carcinoma,sorafenib,targeted therapy

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