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      Drug Design, Development and Therapy (submit here)

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      Efficacy and safety of apatinib combined with chemotherapy for the treatment of advanced gastric cancer in the Chinese population: a systematic review and meta-analysis

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          Abstract

          Objective

          To systematically evaluate the efficacy and safety of the combination of apatinib targeted therapy and chemotherapy (CT) in the treatment of patients with advanced gastric cancer (GC).

          Materials and methods

          Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, EMBASE, CNKI, and the Wanfang database. Outcome measures, including therapeutic efficacy, quality of life (QOL), and adverse events, were extracted and evaluated.

          Results

          Nineteen trials, including 1,256 advanced GC patients, were included. The results indicated that, compared with CT alone, the combination of apatinib targeted therapy with CT significantly improved the patients’ complete response rate (OR=1.85, 95% CI=1.04–3.28, P=0.04), partial response rate (OR=2.19, 95% CI=1.71–2.80, P<0.00001), overall response (OR=2.57, 95% CI=1.99–3.32, P<0.00001), and disease control rate (OR=3.46, 95% CI=2.57–4.66, P<0.00001). Moreover, the combined therapy exhibited advantages over CT alone in the patients’ QOL including the QOL improved rate (OR=1.77, 95% CI=0.94–3.33, P=0.08) and the Karnofsky performance score (OR=1.77, 95% CI=0.94–3.33, P=0.08). The group that received the combined therapy had higher rates of hypertension (OR=5.75, 95% CI=2.22–14.92, P=0.0003), albuminuria (OR=15.42, 95% CI=5.39–44.10, P<0.00001), and hand–foot syndrome (OR=2.09, 95% CI=1.26–3.48, P=0.004), whereas analyses of other adverse events, such as leucopenia, thrombocytopenia, and neutropenia, did not reveal significant differences ( P>0.05).

          Conclusion

          The combination of apatinib targeted therapy and CT is more effective for GC treatment than CT alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria, and hand–foot syndrome. Therefore, the benefits and risks should be considered before treatment.

          Most cited references34

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            Clinical advances in the development of novel VEGFR2 inhibitors.

            Angiogenesis inhibitors have produced significant advances in the treatment of several tumors including colorectal, lung, ovarian and renal carcinomas. These agents, however, modestly impact on the overall cure rate, and their activity is often limited because of the early outbreak of redundant pathways or resistance mechanisms. Moreover, no clear predictive factor has been identified for treatment selection in the clinic. Preclinical evidence suggest that antibodies targeting the vascular endothelial growth factor (VEGF) axis may exert their activity throughout the inhibition of VEGF receptor 2 (VEGFR2) phosphorylation, a key factor in the cancer angiogenic process. Among other molecules, ramucirumab, an intravenously administered, fully humanized monoclonal antibody (mAb) targeting the extracellular domain of the receptor, and apatinib, a potent oral inhibitor of the intracellular domain, are emerging as original antiangiogenic opportunities. This up-to-date review focuses on the development of VEGFR2 inhibitors across multiple cancers and presents results of the most recent researches, ranging from early phase I studies to randomized phase III trials, in which those drugs have been tested as a single-agent or in combination with different chemotherapy regimens.
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              Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-analysis

              Chimeric antigen receptor (CAR) modified T cells targeted CD19 showed promising clinical outcomes in treatment of B cell malignances such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) and other indolent lymphomas. However, the clinical benefit varies tremendously among different trials. This meta-analysis investigated the efficacy (response rates and survival time) of CD19-CAR T cells in refractory B cell malignances in Phase I clinical trials. We searched publications between 1991 and 2014 from PubMed and Web of Science. Pooled response rates were calculated using random-effects models. Heterogeneity was investigated by subgroup analysis and meta-regression. Fourteen clinical trials including 119 patients were eligible for response rate evaluation, 62 patients in 12 clinical trials were eligible for progression-free survival analysis. The overall pooled response rate of CD19-CAR T cells was 73% (95% confidence interval [CI]: 46-94%). Significant heterogeneity across estimates of response rates was observed (p < 0.001, I2=88.3%). ALL patients have higher response rate (93%, 95% CI: 65-100%) than CLL (62%, 95% CI: 27-93%) and lymphoma patients (36%, 95% CI: 1-83%). Meta-regression analysis identified lymphodepletion and no IL-2 administrated T cells as two key factors associated with better clinical response. Lymphodepletion and higher infused CAR T cell number were associated with better prognosis. In conclusion, this meta-analysis showed a high clinical response rate of CD19-CAR T cell-based immunotherapy in treatment of refractory B cell malignancies. Lymphodepletion and increasing number of infused CD19-CAR T cells have positive correlations with the clinical efficiency, on the contrary, IL-2 administration to T cells is not recommended.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                11 July 2018
                : 12
                : 2173-2183
                Affiliations
                [1 ]Department of Gastroenterological Surgery, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, Shandong Province, People’s Republic of China
                [2 ]Department of Clinical Laboratory, Liaocheng People’s Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng 252000, Shandong Province, People’s Republic of China
                [3 ]Department of Clinical Laboratory, Yidu Central Hospital of Weifang, Qingzhou 262500, Shandong Province, People’s Republic of China
                [4 ]Department of Health, Liaocheng People’s Hospital of Taishan Medical University, Liaocheng 252000, Shandong Province, People’s Republic of China, mmzhangyc@ 123456163.com
                Author notes
                Correspondence: Yucai Zhang, Department of Health, Liaocheng People’s Hospital of Taishan Medical University, Dongchang West Road 67, Liaocheng 252000, Shandong Province, People’s Republic of China, Tel +86 188 6527 1910, Email mmzhangyc@ 123456163.com
                Article
                dddt-12-2173
                10.2147/DDDT.S170678
                6047854
                92da8e73-1c8e-4531-b230-9d625e9ebf21
                © 2018 Cheng 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
                Original Research

                Pharmacology & Pharmaceutical medicine
                apatinib,target therapy,chemotherapy,gastric cancer,meta-analysis

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