如意金黄散联合ICIs治疗肝癌晚期伴肝胆湿热证者的临床观察

Clinical observation of Ruyi jinhuang powder combined with ICIs in the treatment of advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder

目的探讨如意金黄散外敷联合免疫检查点抑制剂(ICIs)治疗肝癌晚期伴肝胆湿热证患者的临床效果及安全性。方法选择2018年1月至2022年6月在我院就诊的肝癌晚期伴肝胆湿热证患者,按随机数字表法分为观察组和对照组,对照组56例患者采用ICIs(纳武利尤单抗注射液/信迪利单抗注射液/注射用卡瑞利珠单抗)200 mg静脉滴注治疗,每21 d为1个周期;观察组56例患者在对照组治疗基础上给予如意金黄散外敷,每日1次。治疗1个周期后比较两组患者的疗效;观察两组患者治疗前后血清中白细胞介素6(IL-6)、基质金属蛋白酶9(MMP-9)、环氧合酶2(COX-2)、前列腺素E2(PGE2)、糖类抗原199(CA199)、甲胎蛋白(AFP)和血管内皮生长因子(VEGF)的水平,两组患者Karnofsky功能状态(KPS)评分、数字评定量表(NRS)评分、中医总症状积分,并记录不良反应发生情况。结果治疗后,观察组患者血清中IL-6、MMP-9、COX-2、PGE2、CA199、AFP、VEGF水平及NRS评分、中医总症状积分均显著低于对照组(P<0.05);KPS评分显著高于对照组(P<0.05)。观察组患者的总有效率和总缓解率分别为64.29%、80.36%,对照组分别为60.71%、73.21%,两组比较差异均无统计学意义(P>0.05)。两组患者的不良反应均以恶心呕吐、肝功能损伤、发热等为主,观察组不良反应发生率显著低于对照组(P<0.05)。结论对于肝癌晚期伴肝胆湿热证的患者而言,采用如意金黄散外敷联合ICIs治疗有助于抑制疼痛介质分泌,调节血管内皮功能,减轻炎症反应,促进心肺功能恢复,提高临床疗效,且安全性较高。

OBJECTIVE To explore the clinical efficacy and safety of Ruyi jinhuang powder for external application combined with immune checkpoint inhibitors(ICIs)in the treatment of patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder.METHODS All patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder were admitted to our hospital from January 2018 to June 2022 and assigned into observation group and control group according to random number table method.Patients in the control group(n=56)were treated with ICIs(Navulizumab injection/Sintilimab injection/Camrelizumab for injection)200 mg,ivgtt,21 days as a treatment cycle.Patients in the observation group(n=56)were additionally treated with Ruyi jinhuang powder for external application,once a day,on the basis of control group.The therapeutic effects of 2 groups were compared after a treatment cycle.The levels of interleukin-6(IL-6),matrix metalloproteinase-9(MMP-9),cyclooxygenase-2(COX-2),prostaglandin E2(PGE2),carbohydrate antigen 199(CA199),alpha-fetoprotein(AFP)and vascular endothelial growth factor(VEGF)in serum were compared between 2 groups before and after treatment.Karnofsky functional status(KPS)score,digital rating scale(NRS)score,total symptom score of traditional Chinese medicine,and the occurrence of adverse reactions were recorded for both groups of patients.RESULTS After treatment,the levels of IL-6,MMP-9,COX-2,PGE2,CA199,AFP,VEGF,NRS score and total symptom score of traditional Chinese medicine in observation group were significantly lower than control group(P<0.05),KPS score was significantly higher than the control group(P<0.05).The total effective rate and remission rate of the observation group were 64.29%and 80.36%,those of control group were 60.71%and 73.21%.There was no statistical significance between two groups(P>0.05).The adverse drug reactions of both groups were mainly nausea and vomiting,liver function injury,fever and so on;the incidence of adverse reaction in observation group was significantly lower than that of control group(P<0.05).CONCLUSIONS In patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder,the combination of Ruyi jinhuang powder for external application and ICIs can help inhibit the secretion of pain mediators,regulate vascular endothelial function,reduce the inflammatory response,promote the recovery of cardiopulmonary function,improve clinical efficacy and has good safety.