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阿帕替尼联合卡瑞利珠单抗治疗中晚期肝细胞癌的疗效及其对患者免疫功能、肿瘤标志物的影响OA北大核心CSTPCD

Efficacy of apatinib combined with camrelizumab in the treatment of advanced hepatocellular carcinoma and its impact on patients'immune function and tumor markers

中文摘要英文摘要

背景与目的:近年来靶向药物治疗迅速发展,已成为治疗晚期肝细胞癌(HCC)的重要手段.但一线靶向药物索拉非尼治疗HCC应答率低,靶向药物治疗HCC的临床方案仍是一个需要不断提高的难题.本研究探讨阿帕替尼联合卡瑞利珠单抗治疗中晚期HCC的临床疗效,以及对患者免疫功能、肿瘤标志物影响. 方法:回顾性分析2022年5月-12月湖北省中医院收治的137例中晚期不可切除的HCC患者临床资料,其中61例单纯口服阿帕替尼治疗(靶向组),76例在口服阿帕替尼基础上,同时给予卡瑞利珠单抗静脉滴注(靶免组).比较两组客观缓解率(ORR)与疾病控制率(DCR);T淋巴细胞亚群(CD3+、CD4+、CD8+)、甲胎蛋白(AFP)、高尔基体蛋白73(GP-73)、甲胎蛋白异质体3(AFP-L3)水平;肝肾功能指标与不良反应情况;随访12个月,统计两组患者的无进展生存(PFS)情况. 结果:治疗前,两组患者的一般资料、肝肾功能指标、免疫与肿瘤标志物水平差异均无统计学意义(均 P>0.05).治疗后,靶免组 ORR 与 DCR 均高于靶向组(40.79%vs.16.39%,P=0.02;60.53%vs.39.34%,P=0.014);靶免组CD3+、CD4+、CD4+/CD8+高于靶向组,CD8+低于靶向组(均P<0.05);靶免组AFP、GP-73、AFP-L3低于靶向组(均P<0.05);靶免组总胆红素、丙氨酸氨基转移酶水平低于靶向组(均P<0.05);靶免组皮肤毛细血管增生症发生率高于靶向组(42.11%vs.18.03%,P<0.05),其余不良反应发生率两组间差异均无统计学意义(均P>0.05).两组均随访12个月,靶免组中位PFS明显长于靶向组(10 个月vs.6个月,x2=9.954,P<0.05). 结论:阿帕替尼联合卡瑞利珠单抗治疗HCC可上调T淋巴细胞水平,降低肿瘤标志物水平,有效延长生存时间,疗效优于单纯靶向治疗,且安全性良好.

Background and Aims:In recent years,targeted drug therapy has rapidly developed and become an important method for treating advanced hepatocellular carcinoma(HCC).However,the response rate of first-line targeted drug sorafenib in treating HCC is low,and improving clinical protocols for targeted drug therapy in HCC remains a challenging issue.This study was performed to investigate the clinical efficacy of apatinib combined with camrelizumab in treating intermediate to advanced HCC and its impact on patients'immune function and tumor markers. Methods:The clinical data of 137 patients with unresectable intermediate to advanced HCC admitted between May and December 2022 were retrospectively analyzed.Among them,61 patients were treated with oral apatinib alone(targeted group),and 76 received intravenous camrelizumab in addition to oral apatinib(targeted-immune group).The objective response rate(ORR)and disease control rate(DCR)of the two groups were compared;levels of T lymphocyte subsets(CD3+,CD4+,CD8+),alpha-fetoprotein(AFP),Golgi protein 73(GP-73),and AFP-L3 were measured;liver and kidney function indicators and adverse reactions were monitored.A 12-month follow-up was conducted to assess the two groups'progression-free survival(PFS). Results:Before treatment,there were no statistically significant differences in general data,liver and kidney function indicators,and immune and tumor marker levels between the two groups(all P>0.05).After treatment,the ORR and DCR in the targeted-immune group were higher than those in the targeted group(40.79%vs.16.39%,P=0.02;60.53%vs.39.34%,P=0.014).The CD3+,CD4+,and CD4+/CD8+levels in the targeted-immune group were higher,while CD8+levels were lower than those in the targeted group(all P<0.05).AFP,GP-73,and AFP-L3 levels in the targeted-immune group were lower than those in the targeted group(all P<0.05).The total bilirubin and alanine aminotransferase levels in the targeted-immune group were lower than those in the targeted group(both P<0.05).The incidence of skin capillary hemangiomas was higher in the targeted-immune group than in the targeted group(42.11%vs.18.03%,P<0.05).In contrast,the incidence of other adverse reactions did not differ significantly between the two groups(all P>0.05).After 12 months of follow-up,the median PFS in the targeted-immune group was significantly longer than that in the targeted group(10 months vs.6 months,x2=9.954,P<0.05). Conclusion:Apatinib combined with camrelizumab in treating HCC can enhance T lymphocyte levels,reduce tumor marker levels,effectively prolong survival time,and have better efficacy than targeted therapy alone,with reasonable safety.

黄大伟;江诗怡;厉晶萍;常玉娟;蒋满红

湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院肝病科,湖北武汉 430074||湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院肿瘤科,湖北武汉 430074||湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院湖北时珍试验室,湖北武汉 430074||湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院中医肝肾研究及应用重点试验室,湖北武汉 430074湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院肿瘤科,湖北武汉 430074||湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院湖北时珍试验室,湖北武汉 430074||湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院中医肝肾研究及应用重点试验室,湖北武汉 430074湖北省中医院/湖北中医药大学附属医院/湖北省中医药研究院肿瘤科,湖北武汉 430074

临床医学

癌,肝细胞;抗肿瘤联合化疗方案;阿帕替尼;卡瑞利珠

Carcinoma,Hepatocellular;Antineoplastic Combined Chemotherapy Protocols;Apatinib;Camrelizumab

《中国普通外科杂志》 2024 (007)

1070-1077 / 8

湖北省科技厅科技计划基金资助项目(2023BCB126).

10.7659/j.issn.1005-6947.2024.07.006

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