FOLFOX4、SOX化疗方案治疗晚期胃癌的疗效及对血清生物活性因子及预后的影响
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摘要
目的探讨奥沙利铂+亚叶酸钙+5-氟尿嘧啶(FOLFOX4)、奥沙利铂+替吉奥(SOX)化疗方案治疗晚期胃癌的疗效及对血清基质金属蛋白酶9(MMP9)、CD44v6、血管内皮细胞生长因子C(VEGFC)、转化生长因子-β1(TGF-β1)水平和预后的影响。方法根据治疗方法不同将112例晚期胃癌患者分为对照组与观察组,每组56例。对照组患者采用FOLFOX4方案化疗,观察组患者采用SOX方案化疗。比较两组患者的近期疗效、远期生存情况、不良反应发生情况,并对两组患者治疗前后的血清MMP9、CD44v6、VEGFC、TGF-β1水平进行比较。结果治疗结束后,两组患者的疾病控制率、客观缓解率比较,差异均无统计学意义(P﹥0.05)。化疗过程中,两组患者白细胞减少、血小板减少、乏力、恶心、呕吐、口腔黏膜炎、肝肾功能不全、神经功能异常的发生率比较,差异均无统计学意义(P﹥0.05)。两组患者治疗后的血清MMP9、CD44v6、VEGFC、TGF-β1水平均明显低于本组治疗前(P﹤0.01);观察组患者治疗后的血清MMP9、CD44v6、VEGFC、TGF-β1水平均低于对照组治疗后(P﹤0.05)。观察组患者的2年生存率高于对照组(P﹤0.05)。结论 SOX化疗方案治疗晚期胃癌的远期疗效优于FOLFOX4方案,可能与降低血清MMP9、CD44v6、VEGFC、TGF-β1水平有关。
Objective To observe the effects of chemotherapy applying oxalipatin + calcium folinate + 5-fluorouracil(FOLFOX4) or oxalipatin + tegafur/gimeracil/oteracil(SOX) in advanced gastric carcinoma and their influence on serum levels of matrix metalloproteinase-9(MMP9), CD44v6, vascular epithelial growth factor C(VEGFC), transforming growth factor β1(TGF-β1) and prognosis. Method A total of 112 cases with advanced gastric carcinoma treated by different therapies were included in the study as control group and study group, with 56 cases in each, respectively. The control group was treated with FOLFOX4 regimen, and study group with SOX regimen. The short-term efficacy, long-term survival, adverse reactions and serum levels of MMP9, CD44v6, VEGFC, and TGF-β1 before and after treatment were compared between the two groups. Result After treatment, the disease control rate and objective response rate in both groups were of no statistically significant differences(P>0.05). During chemotherapy, there were no significant differences regarding the incidence of leukopenia, thrombocytopenia, fatigue, nausea, vomiting, oral mucositis, liver and kidney dysfunction and neurological abnormalities between the two groups(P>0.05). The levels of serum MMP9, CD44v6,VEGFC and TGF-β1 in the two groups after treatment were significantly decreased compared to that before treatment(P<0.01); and the levels of serum MMP9, CD44v6, VEGFC and TGF-β1 in study group were significantly lower than those in control group after treatment(P<0.05). The 2-year survival rate in study group was significantly higher than that in control group(P<0.05). Conclusion The long-term efficacy of SOX chemotherapy in the treatment of advanced gastric cancer is better compared to FOLFOX4 regimen, which may be related to the reduction of serum levels of MMP9, CD44v6,VEGFC and TGF-β1.
Objective To observe the effects of chemotherapy applying oxalipatin + calcium folinate + 5-fluorouracil(FOLFOX4) or oxalipatin + tegafur/gimeracil/oteracil(SOX) in advanced gastric carcinoma and their influence on serum levels of matrix metalloproteinase-9(MMP9), CD44v6, vascular epithelial growth factor C(VEGFC), transforming growth factor β1(TGF-β1) and prognosis. Method A total of 112 cases with advanced gastric carcinoma treated by different therapies were included in the study as control group and study group, with 56 cases in each, respectively. The control group was treated with FOLFOX4 regimen, and study group with SOX regimen. The short-term efficacy, long-term survival, adverse reactions and serum levels of MMP9, CD44v6, VEGFC, and TGF-β1 before and after treatment were compared between the two groups. Result After treatment, the disease control rate and objective response rate in both groups were of no statistically significant differences(P>0.05). During chemotherapy, there were no significant differences regarding the incidence of leukopenia, thrombocytopenia, fatigue, nausea, vomiting, oral mucositis, liver and kidney dysfunction and neurological abnormalities between the two groups(P>0.05). The levels of serum MMP9, CD44v6,VEGFC and TGF-β1 in the two groups after treatment were significantly decreased compared to that before treatment(P<0.01); and the levels of serum MMP9, CD44v6, VEGFC and TGF-β1 in study group were significantly lower than those in control group after treatment(P<0.05). The 2-year survival rate in study group was significantly higher than that in control group(P<0.05). Conclusion The long-term efficacy of SOX chemotherapy in the treatment of advanced gastric cancer is better compared to FOLFOX4 regimen, which may be related to the reduction of serum levels of MMP9, CD44v6,VEGFC and TGF-β1.
引文
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[13]Radu EC,Saizu AI,Grigorescu RR,et al.Metastatic neuroendocrine pancreatic tumor-case report[J].J Med Life,2018,11(1):57-61.
[14]Li F,Wang Y,Li C,et al.Comparison of clinicopathological features and prognosis analysis between carcinoma in the remnant stomach and gastric cancer[J].Zhonghua Wei Chang Wai Ke Za Zhi,2018,21(5):529-534.
[15]刘威,顾康生,李敏,等.晚期胃癌含铂方案化疗疗效与miR-192表达水平的研究[J].安徽医科大学学报,2016,51(7):1027-1031.
[16]王磊,汪建平.结直肠癌腹膜转移的研究现状及其争议[J].中华实验外科杂志,2014,31(2):234-235.
[17]Azarkhazin F,Tehrani GA.Detecting promoter methylation pattern of apoptotic genes apaf1 and caspase8 in gastric carcinoma patients undergoing chemotherapy[J].JGastrointest Oncol,2018,9(2):295-302.
[18]宾业鸿,蔡正文,刘汉峰.SOX方案与改良mFOLFOX6方案治疗弥散型进展期胃癌的疗效和安全性比较[J].中国药房,2016,27(21):2903-2906.
[19]刘静,刘婷,徐睿玲,等.SN50联合5-氟尿嘧啶通过调节NF-κB信号通路抑制人胃癌裸鼠移植瘤生长的研究[J].胃肠病学和肝病学杂志,2016,25(1):5-8.
[20]李雅冰.SOX方案与FOLFOX4方案治疗进展期胃癌的临床疗效和安全性探讨[J].中国医药指南,2014,12(23):200-201.
[21]党进胜,赵新汉.替吉奥联合奥沙利铂在进展期胃癌患者中的应用价值[J].实用癌症杂志,2014,29(7):775-778.
[22]李志玖,艾淑颖,宋先波.替吉奥胶囊单药治疗晚期胃癌的临床观察[J].实用癌症杂志,2013,28(1):56-57.
[23]翁伟明,张涛,凌亚非,等.SOX方案与FOLFOX4方案治疗进展期胃癌临床效果和安全性[J].中国医药导报,2013,10(18):72-73;76.
[24]徐迅,张长乐.奥沙利铂联合卡培他滨新辅助化疗方案在ⅡB~ⅢC期胃癌中的应用[J].安徽医药,2015,19(5):978-981.
[25]陈晓露,罗昊,吴蓉宜.胃癌合并Hp-L感染患者MIF和MMP9表达变化及其与血清炎症因子的关系[J].重庆医学,2017,46(2):250-253.
[26]于海东,辛华,王英,等.胃癌患者血清中骨桥蛋白和CD44v6检测的临床意义[J].中国全科医学,2012,15(6):648-650.
[27]Komiyama S,Izumiya Y,Kimura Y,et al.A distal bile duct carcinoma patient who underwent surgical resection for liver metastasis[J].Gan To Kagaku Ryoho,2018,45(3):560-562.
[28]安燕芳,张魁,徐云,等.胃癌患者血清转化生长因子β1、癌胚抗原和糖链抗原19-9检测的临床价值[J].临床荟萃,2007,22(23):1691-1693.
[29]孙云,马国娟,胡晓杰,等.TGF-β1促进人胃癌MKN28细胞上皮-间质转化和转移的研究[J].重庆医学,2018,47(11):1444-1448.
[2]Roviello G,Petrioli R,Nardone V,et al.Docetaxel,oxaliplatin,5FU,and trastuzumab as first-line therapy in patients with human epidermal receptor 2-positive advanced gastric or gastroesophageal junction cancer:preliminary results of a phase II study[J].Medicine(Baltimore),2018,97(20):e10745.
[3]董富宏,梁海侠.芪苈强心胶囊对糖尿病合并心力衰竭患者心功能及血管内皮功能的改善作用[J].现代中西医结合杂志,2015,24(25):2792-2794.
[4]宋武,何裕隆.晚期胃癌腹主动脉旁淋巴结转移综合治疗策略[J].中国实用外科杂志,2017,37(10):1102-1106.
[5]Yudong S,Zhaoting M,Xinyue W,et al.EGFR exon 20 insertion mutation in advanced thymic squamous cell carcinoma:response to apatinib and clinical outcomes[J].Thorac Cancer,2018,9(7):885-891.
[6]沈玲,罗波.晚期胃癌二线使用EOX和FOLFIRI方案化疗的疗效及安全性评价[J].西安交通大学学报(医学版),2018,39(4):546-550.
[7]任晓晓,张小茜,张红梅,等.塞来昔布联合FOLFOX4方案治疗晚期胃癌的疗效及机制研究[J].中国现代医学杂志,2018,28(15):27-31.
[8]Eisenhauer EA,Therasse P,Bogaerts J,et al.New response evaluation criteria in solid tumours:revised RECIST guideline(version 1.1)[J].Eur J Cancer,2009,45(2):228-247.
[9]皋文君,刘砚燕,袁长蓉.国际肿瘤化疗药物不良反应评价系统--通用不良反应术语标准4.0版[J].肿瘤,2012,32(2):142-144.
[10]Iii BA.Advanced gastric cancer:an update[J].Gastroint Cancer Res,2010,2(Suppl 1):S37-S38.
[11]Hwang GY,Baek DW,Cho HJ,et al.Elevated neutrophilto-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with trastuzumab combination chemotherapy[J].Anticancer Res,2018,38(5):3151-3156.
[12]王海英,郑瑞鹏,姚志华,等.SOX方案与FOLFOX4方案治疗老年晚期胃癌的临床分析[J].中国老年学杂志,2015,35(6):1525-1527.
[13]Radu EC,Saizu AI,Grigorescu RR,et al.Metastatic neuroendocrine pancreatic tumor-case report[J].J Med Life,2018,11(1):57-61.
[14]Li F,Wang Y,Li C,et al.Comparison of clinicopathological features and prognosis analysis between carcinoma in the remnant stomach and gastric cancer[J].Zhonghua Wei Chang Wai Ke Za Zhi,2018,21(5):529-534.
[15]刘威,顾康生,李敏,等.晚期胃癌含铂方案化疗疗效与miR-192表达水平的研究[J].安徽医科大学学报,2016,51(7):1027-1031.
[16]王磊,汪建平.结直肠癌腹膜转移的研究现状及其争议[J].中华实验外科杂志,2014,31(2):234-235.
[17]Azarkhazin F,Tehrani GA.Detecting promoter methylation pattern of apoptotic genes apaf1 and caspase8 in gastric carcinoma patients undergoing chemotherapy[J].JGastrointest Oncol,2018,9(2):295-302.
[18]宾业鸿,蔡正文,刘汉峰.SOX方案与改良mFOLFOX6方案治疗弥散型进展期胃癌的疗效和安全性比较[J].中国药房,2016,27(21):2903-2906.
[19]刘静,刘婷,徐睿玲,等.SN50联合5-氟尿嘧啶通过调节NF-κB信号通路抑制人胃癌裸鼠移植瘤生长的研究[J].胃肠病学和肝病学杂志,2016,25(1):5-8.
[20]李雅冰.SOX方案与FOLFOX4方案治疗进展期胃癌的临床疗效和安全性探讨[J].中国医药指南,2014,12(23):200-201.
[21]党进胜,赵新汉.替吉奥联合奥沙利铂在进展期胃癌患者中的应用价值[J].实用癌症杂志,2014,29(7):775-778.
[22]李志玖,艾淑颖,宋先波.替吉奥胶囊单药治疗晚期胃癌的临床观察[J].实用癌症杂志,2013,28(1):56-57.
[23]翁伟明,张涛,凌亚非,等.SOX方案与FOLFOX4方案治疗进展期胃癌临床效果和安全性[J].中国医药导报,2013,10(18):72-73;76.
[24]徐迅,张长乐.奥沙利铂联合卡培他滨新辅助化疗方案在ⅡB~ⅢC期胃癌中的应用[J].安徽医药,2015,19(5):978-981.
[25]陈晓露,罗昊,吴蓉宜.胃癌合并Hp-L感染患者MIF和MMP9表达变化及其与血清炎症因子的关系[J].重庆医学,2017,46(2):250-253.
[26]于海东,辛华,王英,等.胃癌患者血清中骨桥蛋白和CD44v6检测的临床意义[J].中国全科医学,2012,15(6):648-650.
[27]Komiyama S,Izumiya Y,Kimura Y,et al.A distal bile duct carcinoma patient who underwent surgical resection for liver metastasis[J].Gan To Kagaku Ryoho,2018,45(3):560-562.
[28]安燕芳,张魁,徐云,等.胃癌患者血清转化生长因子β1、癌胚抗原和糖链抗原19-9检测的临床价值[J].临床荟萃,2007,22(23):1691-1693.
[29]孙云,马国娟,胡晓杰,等.TGF-β1促进人胃癌MKN28细胞上皮-间质转化和转移的研究[J].重庆医学,2018,47(11):1444-1448.