甲磺酸阿帕替尼联合TACE治疗中晚期肝癌的效果及对患者血清VEGF和MMP-9的影响
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摘要
目的:评价甲磺酸阿帕替尼联合经皮肝动脉化疗栓塞术(TACE)治疗中晚期肝癌的疗效及对血清血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP)-9的影响。方法:选取2015年6月-12月瑞安市人民医院收治的中晚期肝细胞肝癌(HCC)患者46例,随机分为观察组、对照组,各23例,对照组仅采用TACE治疗,观察组在对照组的基础上给予甲磺酸阿帕替尼治疗,比较两组间的疗效、不良反应、血清VEGF及MMP-9水平。结果:观察组的疾病控制率明显高于对照组(56.52%vs. 26.08%,P<0.05);观察组的半年生存率和1年生存率分别为52.17%和34.78%,对照组为34.78%和21.74%,差异均无统计学意义(P>0.05),但观察组的总生存率高于对照组,差异有统计学意义(34.78%vs. 8.69%,P<0.05)。观察组的不良反应发生率为56.5%,与对照组的65.2%差异无统计学意义。治疗前,两组血清VEGF[(232.54±17.05)ng/ml vs.(233.05±15.23)ng/ml]和MMP-9[(1 857.23±15.31)ng/ml vs.(1883.45±15.42)ng/ml]差异均无统计学意义(P>0.05);术后1个月,观察组VEGF低于对照组[(206.04±13.05)ng/ml vs.(225.36±11.42)ng/ml],MMP-9也低于对照组[(1 604.56±15.25)ng/ml vs.(1 835.21±13.58)ng/ml],差异均有统计学意义(P<0.01)。结论:TACE联合甲磺酸阿帕替尼治疗中晚期HCC的疗效优于单纯TACE。
Objective: To evaluate the efficacy of apatinib mesylate combined with TACE in the treatment of advanced hepatocellular carcinoma(HCC) and its effect on serum levels of vascular endothelial growth factor(VEGF) and matrix metalloprotein-9(MMP-9). Methods: Forty-six patients with advanced HCC were randomly divided into observation group and control group from June to December 2015. The patients in control group were treated with TACE only, and the patients in observation group were treated with apatinib mesylate on the basis of the control group. The efficacy, adverse reactions, serum levels of VEGF and MMP-9 were compared between the two groups. Results: The disease control rate of the observation group was significantly higher than that of the control group(P<0.05); the half-year survival rate and the one-year survival rate of the observation group were 52.17% and 34.78%, respectively, and those of the control group were 34.78% and 21.74%. There was no significant difference(P>0.05), but the total survival rate of the observation group was higher than that of the control group, and the difference was statistically significant(P<0.05). The incidence of adverse reactions was similar between the two groups, and there was no significant difference between the two groups. After operation, the levels of VEGF and MMP-9 in the observation group were(206.04 ±13.05) ng/ml and(1 604.56 ±15.25) ng/ml, while those in the control group were(225.36 ±11.42)ng/ml and(1 835.21±13.58) ng/ml, with significant difference(P<0.05). Conclusions: TACE combined with apatinib mesylate is superior to TACE alone in the treatment of advanced HCC.
Objective: To evaluate the efficacy of apatinib mesylate combined with TACE in the treatment of advanced hepatocellular carcinoma(HCC) and its effect on serum levels of vascular endothelial growth factor(VEGF) and matrix metalloprotein-9(MMP-9). Methods: Forty-six patients with advanced HCC were randomly divided into observation group and control group from June to December 2015. The patients in control group were treated with TACE only, and the patients in observation group were treated with apatinib mesylate on the basis of the control group. The efficacy, adverse reactions, serum levels of VEGF and MMP-9 were compared between the two groups. Results: The disease control rate of the observation group was significantly higher than that of the control group(P<0.05); the half-year survival rate and the one-year survival rate of the observation group were 52.17% and 34.78%, respectively, and those of the control group were 34.78% and 21.74%. There was no significant difference(P>0.05), but the total survival rate of the observation group was higher than that of the control group, and the difference was statistically significant(P<0.05). The incidence of adverse reactions was similar between the two groups, and there was no significant difference between the two groups. After operation, the levels of VEGF and MMP-9 in the observation group were(206.04 ±13.05) ng/ml and(1 604.56 ±15.25) ng/ml, while those in the control group were(225.36 ±11.42)ng/ml and(1 835.21±13.58) ng/ml, with significant difference(P<0.05). Conclusions: TACE combined with apatinib mesylate is superior to TACE alone in the treatment of advanced HCC.
引文
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[2]中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[3]王建华.肝癌综合介入治疗的现状[J].中华肝脏病杂志,2005,13(10):721-723.
[4]郭斌,吴增城,张宪光,等.肝动脉栓塞化疗治疗肝癌的应用进展[J].中华肝胆外科杂志,2016,22(2):137-141.
[5]张磊.原发性肝癌介入治疗的研究现状[J].医学综述,2014,20(8):1392-1394.
[6]Wu H,Ding ZH,Hu DQ,et al.Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death[J].J Pathol,2012,227(2):189-199.
[7]金鑫荔,卢伟.TACE联合阿帕替尼治疗中晚期肝细胞癌[J].中国介入影像与治疗学,2017,14(4):200-204.
[8]Folkman J.Tumor angiogenesis:therapeutic implications[J].N Engl J Med,1971,285(21):1182-1186.
[9]Hanahan D,Folkman J.Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis[J].Cell,1996,86(3):353-364.
[10]Dumont DJ,Yamaguchi TP,Conlon RA,et al.Tek,a novel tyrosine kinase gene located on mouse chromosome 4,is expressed in endothelial cells and their presumptive precursors[J].Oncogene,1992,7(8):1471-1480.
[11]Borg JP,deLapeyrière O,Noguchi T,et al.Biochemical characterization of two isoforms of FLT4,a VEGF receptor-related tyrosine kinase[J].Oncogene,1995,10(5):973-984.
[12]Mohamed A,Chenna A,Abdelfatah M,et al.Microvessel density analysis in patients with viral hepatitis-related hepatocellular carcinoma[J].J Gastrointest Cancer,2015,46(2):104-108.
[13]Kasprzak A,Surdacka A,Tomczak M,et al.Expression of angiogenesis-stimulating factors(VEGF,CD31,CD105)and angiogenetic index in gingivae of patients with chronic periodontitis[J].Folia Histochem Cytobiol,2012,50(4):554-564.
[14]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[15]Shim JH,Park JW,Kim JH,et al.Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients[J].Cancer Sci,2008,99(10):2037-2044.
[16]Weder W,Kestenholz P,Taverna C,et al.Neoadjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma[J].J Clin Oncol,2004,22(17):3451-3457.
[17]Zheng J,Shao G,Luo J.Analysis of survival factors in patients with intermediate-advanced hepatocellular carcinoma treated with transcatheter arterial chemoembolization combined with sorafenib[J].Clin Transl Oncol,2014,16(11):1012-1017.
[18]Qin SK.Apatinib in Chinese patients with advanced hepatocellular carcinoma:A phase II randomized,open-label trial[J].JCO,2014,32(15_suppl):4019.
[19]李威,满文玲,郭欢庆,等.TACE联合甲磺酸阿帕替尼治疗中晚期肝癌的临床研究[J].肿瘤药学,2017,7(1):74-78.