晚期肝细胞癌采用帕博利珠单抗联合FOLFOX4化疗效果分析及对VEGF、TGF-β1、bFGF的影响  

Pembrolizumab combined with FOLFOX4 chemotherapy for treatment of advanced hepatocellular carcinoma:Clinical efficacy and impact on serum levels of VEGF,TGF-β1,and bFGF

作　　者：郑志勇[1] 何晓乐 Zhi-Yong Zheng;Xiao-Le He(Department of Pharmacy,Wenzhou Hospital of Traditional Chinese Medicine,Wenzhou 325000,Zhejiang Province,China)

机构地区：[1]温州市中医院药剂科,浙江省温州市325000

出　　处：《世界华人消化杂志》2022年第11期504-510,共7页World Chinese Journal of Digestology

摘　　要：背景由于肝癌发病较隐匿,起病早期常无典型症状与体征,但其同时具有侵袭性高、生长速度快的特点,约70%患者在疾病确诊时已进展到中晚期,丧失手术根治最佳时机,一般推荐行姑息与保守治疗.目的观察晚期肝细胞癌采用帕博利珠单抗联合奥沙利铂、氟尿嘧啶、亚叶酸钙(FOLFOX4)化疗效果分析及对血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、碱性成纤维细胞生长因子(alkaline Fibroblast growth factor,bFGF)的影响.方法选取2019-06/2021-02我院晚期肝细胞癌患者62例,双盲法随机分组,分为观察组(n=31)、对照组(n=31).对照组予以FOLFOX4化疗,观察组在对照组基础上给予帕博利珠单抗,均治疗12 wk.比较两组治疗12wk后临床疗效、生存质量与治疗前、治疗6 wk、12 wk后血管生成有关因子(VEGF、TGF-β1、bFGF)、肿瘤标志物[甲胎蛋白(alpha-fetoprotein,AFP)、糖链抗原199(carbohydrate antigen 199,CA199)、癌胚抗原(carcinoembryonic antigen,CEA)]、miR-143、miR-145表达,并统计不良反应发生情况.结果观察组治疗12 wk后疾病控制率、生存质量改善率分别为87.10%、64.52%,高于对照组的64.52%、38.71%(P<0.05);观察组治疗6 wk、12 wk后血清VEGF、TGF-β1、bFGF、AFP、CA199、CEA、miR-143、miR-145水平均低于对照组(P<0.05);两组神经毒性、肝肾毒性、骨髓抑制、胃肠道反应、手足综合征、免疫相关性肺炎、甲状腺功能减退发生率相比,差异无统计学意义(P>0.05);观察组皮肤过敏反应发生率较对照组高(P<0.05).结论与FOLFOX4方案相比,应用帕博利珠单抗联合FOLFOX4化疗治疗晚期肝细胞癌可更为有效地抑制肿瘤血管生成因子、肿瘤标志物及miR-143、miR-145表达水平,进而提升肿瘤疾病控制率及患者生存质量,但需注意防范皮肤过敏反应等不良反应.BACKGROUND Due to the insidious onset of liver cancer,there are often no typical symptoms and signs at the early stage of the disease,though it is also characterized by high invasiveness and fast growth.About 70%of patients have middle and late stages of the disease when the disease is diagnosed,losing the best opportunity for radical surgery.Palliative and conservative treatment is generally recommended.AIM To observe the effect of pembrolizumab combined with FOLFOX4 chemotherapy in the treatment of advanced hepatocellular carcinoma and its effect on serum levels of angiogenesis-related factors[vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),and basic fibroblast growth factor(bFGF)].METHODS A total of 62 patients with advanced hepatocellular carcinoma at our hospital from June 2019 to February 2021 were selected and randomly divided into either an observation group(n=31)or a control group(n=31)using a double-blind method.Both groups were given FOLFOX4 chemotherapy,and the observation group was additionally given pembrolizumab.The treatment lasted 12 wk in both groups.The clinical efficacy,quality of life,the serum levels of angiogenesis-related factors(VEGF,TGF-β1,and bFGF),tumor markers[alpha-fetoprotein(AFP),carbohydrate antigen 199(CA199),and carcinoembryonic antigen(CEA)],miR-143,and miR-145,and adverse reactions compared between the two groups.RESULTS After 12 wk of treatment,the disease control rate and the improvement rate of quality of life in the observation group were 87.10%and 64.52%,respectively,which were higher than those of the control group(64.52%and 38.71%,respectively;P<0.05).Serum VEGF,TGF-β1,bFGF,AFP,CA199,CEA,miR-143,and miR-145 levels in the observation group after 6 and 12 wk of treatment were all lower than those in the control group(P<0.05).There was no significant difference in the incidence of neurotoxicity,hepatorenal toxicity,bone marrow suppression,gastroin-testinal reaction,hand foot syndrome,immune associated pneumonia,or hypothyroidism between t

关 键 词：帕博利珠单抗 奥沙利铂 卡培他滨 晚期肝细胞癌 肿瘤血管生成因子 MIR-143 MIR-145 

分 类 号：R735.7[医药卫生—肿瘤]