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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Apatinib combined with docetaxel as a salvage treatment for metastatic esophageal squamous cancer: a case report

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          Abstract

          The first-line treatment for metastatic esophageal squamous cell cancer (ESCC) is a platinum- or fluorouracil-based agent, followed by later treatment with taxanes or irinotecan. However, there is still no standard third-line treatment for patients with metastatic ESCC. We present a 62-year-old man initially diagnosed with locally advanced ESCC. After esophagectomy, the patient was administrated with six cycles of docetaxel and cisplatin combined with radiotherapy. After 8.0 months, computed tomography showed the left cervical lymph node metastasis. However, the metastatic lymph node was not significantly shrunk after locally palliative radiotherapy and the patient was intolerant of irinotecan as second-line systemic therapy. Then, the patient was rechallenged with six cycles of docetaxel combined with apatinib (an oral tyrosine kinase inhibitor to vascular endothelial growth factor receptor 2 [VEGFR2]), followed by single dose of apatinib as maintenance therapy. According to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard, partial response was achieved in this case after treating with docetaxel combined with apatinib. Now, the progression-free survival of this patient has been 7.5 months. After administrating with apatinib for 2 weeks, hypertension (grade III) was observed. Thus, the dose of apatinib was decreased from 850 to 500 mg and then the adverse effects were controllable and tolerable. In conclusion, apatinib with concurrent docetaxel provided potential efficacy as a salvage treatment for patients with metastatic ESCC. To our knowledge, this is the first case of ESCC who responded to apatinib combined with docetaxel.

          Most cited references23

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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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            Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

            Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS. © 2014 UICC.
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              Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters.

              Apatinib, a small-molecule multitargeted tyrosine kinase inhibitor, is in phase III clinical trial for the treatment of patients with non-small-cell lung cancer and gastric cancer in China. In this study, we determined the effect of apatinib on the interaction of specific antineoplastic compounds with P-glycoprotein (ABCB1), multidrug resistance protein 1 (MRP1, ABCC1), and breast cancer resistance protein (BCRP, ABCG2). Our results showed that apatinib significantly enhanced the cytotoxicity of ABCB1 or ABCG2 substrate drugs in KBv200, MCF-7/adr, and HEK293/ABCB1 cells overexpressing ABCB1 and in S1-M1-80, MCF-7/FLV1000, and HEK293/ABCG2-R2 cells overexpressing ABCG2 (wild-type). In contrast, apatinib did not alter the cytotoxicity of specific substrates in the parental cells and cells overexpressing ABCC1. Apatinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin in the multidrug resistance (MDR) cells. Furthermore, apatinib significantly inhibited the photoaffinity labeling of both ABCB1 and ABCG2 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner. The ATPase activity of both ABCB1 and ABCG2 was significantly increased by apatinib. However, apatinib, at a concentration that produced a reversal of MDR, did not significantly alter the ABCB1 or ABCG2 protein or mRNA expression levels or the phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Importantly, apatinib significantly enhanced the effect of paclitaxel against the ABCB1-resistant KBv200 cancer cell xenografts in nude mice. In conclusion, apatinib reverses ABCB1- and ABCG2-mediated MDR by inhibiting their transport function, but not by blocking the AKT or ERK1/2 pathway or downregulating ABCB1 or ABCG2 expression. Apatinib may be useful in circumventing MDR to other conventional antineoplastic drugs. ©2010 AACR.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                13 September 2018
                : 11
                : 5821-5826
                Affiliations
                [1 ]Department of Radiation Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, People’s Republic of China, jxdysy1970@ 123456163.com
                [2 ]Tumor Laboratory, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, People’s Republic of China, jxdysy1970@ 123456163.com
                Author notes
                Correspondence: Xiao-Dong Jiang, Department of Radiation Oncology, Tumor Laboratory, The Affiliated Lianyungang Hospital of Xuzhou Medical University, NO 182 Tongguan North Road, Lianyungang 222002, Jiangsu Province, People’s Republic of China, Tel +86 518 8560 5722, Fax +86 518 8545 6700, Email jxdysy1970@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                ott-11-5821
                10.2147/OTT.S174429
                6145360
                837ec17d-64b7-487b-bf4f-c8d1e0dea0aa
                © 2018 Liang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Case Report

                Oncology & Radiotherapy
                metastatic esophageal cancer,apatinib,docetaxel,vascular endothelial growth factor receptor-2,anti-angiogenesis

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