龙藤通络方联合阿片类止痛药治疗中重度肺癌癌痛的前瞻性临床研究  

A Prospective Clinical Trial of Longteng Tongluo Formula Combined with Opioid Analgesics for the Treatment of Moderate to Severe Cancer Pain of Lung Cancer

作　　者：周迪 许玲[1,2] 黄虞枫 董昌盛[2,4] 陈建茹 苏羚子 林丹 姚嘉麟 龚亚斌[1] 陈洁[1] ZHOU Di;XU Ling;HUANG Yu-feng;DONG Chang-sheng;CHEN Jian-ru;SU Ling-zi;LIN Dan;YAO Jia-lin;GONG Ya-bin;CHEN Jie(The First Department of Oncology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Oncology Institute of Traditional Chinese Medicine,Shanghai Academy of Traditional Chinese Medicine,Shanghai 200032,China;State Key Laboratory of Traditional Chinese Medicine Syndrome,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Department of Oncology,Longhua hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;General Manager Office,Shanghai Tongjitang Pharmaceutical Co.,Ltd.,Shanghai 201707,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院肿瘤一科,上海200437 [2]上海市中医药研究院中医肿瘤研究所,上海200032 [3]广州中医药大学第二附属医院中医证候全国重点实验室,广东广州510006 [4]上海中医药大学附属龙华医院肿瘤科,上海200032 [5]上海同济堂药业有限公司质量部,上海201707

出　　处：《中医肿瘤学杂志》2024年第2期24-32,共9页Journal of Oncology in Chinese Medicine

基　　金：国家科技重大专项(编号:2019ZX09201004-002-001);上海市科学技术委员会科技计划项目(编号:20S31904100)。

摘　　要：目的观察龙藤通络方外用联合阿片类止痛药治疗中重度肺癌癌痛的临床疗效。方法采用多中心、开放标签的随机对照试验设计,收集中重度肺癌癌痛患者117例(治疗组57例,对照组60例),治疗组采用阿片类药物联合龙藤通络方外用,对照组采用单纯阿片类药物,连续给药8天,分别观察两组患者疼痛治疗前后数字疼痛评分法(numerical rating scale,NRS)评分、日均吗啡消耗量、爆发痛次数、止痛起效时间及不良反应,评价镇痛疗效。并运用UPLC-QQQ-MS/MS质谱技术对龙藤通络方含测指标进行检测,预估止痛有效成分。结果治疗组疼痛缓解率97.37%,显效率为50.88%,均高于对照组(P<0.05),治疗组治疗前后NRS评分差值为(2.07±1.02)分,与对照组比较差异有统计学意义(P<0.05)。分层分析显示在不同疼痛程度及类型人群中,龙藤通络方联合阿片类药物对中度疼痛(NRS评分4分~7分)、骨转移性癌痛以及副肿瘤综合征、恶病质等引起的癌痛人群中治疗疗效更有优势,治疗前后NRS差值与同类型对照组有明显差异(P<0.05)。治疗组中度疼痛亚组患者的等效吗啡日均消耗量为(61.57±51.69)mg,少于中度疼痛对照组(P<0.05)。龙藤通络方联合治疗后与外治相关的不良反应以皮肤瘙痒和局部红肿为主,其余发生率超过10%的不良反应主要为恶心呕吐、便秘、头晕、肝肾功能及心电图异常。质谱分析检测出龙藤通络方中野漆树苷、络石苷等7个活性指标性化合物,这些有效成分可能在肺癌癌痛治疗中起着一定作用。结论龙藤通络方联合阿片类止痛方案有协同、增效的作用,尤其在中度疼痛中效果显著,可减少中度疼痛患者阿片类药物日均消耗量,且安全性好。Objective To observe the clinical efficacy of Longteng Tongluo Formula combined with opioid analgesics for the treatment of moderate to severe cancer pain of lung cancer.Methods A multicenter,open-label randomized controlled trial was designed to collect 117 lung cancer patients with moderate to severe pain,with 57 cases in the treatment group and 60 cases in the control group.The treatment group was treated with opioids combined with Longten Tongluo Formula for external use,while the control group was given opioids alone,for successive 8 days.Numerical rating scale(NRS)scores,daily morphine consumption,frequency of pain outbreak,analgesic onset time,and adverse reactions of the two groups were observed before and after treatment to evaluate analgesic efficacy.Furthermore,UPLC-QQQ-MS/MS mass spectrometry was used to detect the content of Longteng Tongluo Formula and estimated the effective analgesic ingredients.Results The pain relief rate of the treatment group was 97.37%and the significant efficiency was 50.88%,which were higher than those of the control group(P<0.05).The difference of NRS scores before and after treatment in the treatment group was(2.07±1.02)points,with statistical significance compared with the control group(P<0.05).Stratified analysis showed that in different pain levels and types of populations,Longteng Tongluo Formula combined with opioids was more effective in treating moderate pain(NRS score of 4 to 7 points)as well as patients with cancer pain caused by bone metastases,paraneoplastic syndromes,cachexia,etc.There was a significant difference in NRS scores before and after treatment compared with the same type of control group(P<0.05).The daily equivalent morphine consumption in the subgroup with moderate pain was(61.57±51.69)mg,which was lower than that in control group with moderate pain(P<0.05).The main adverse reactions related to external treatment of the combination therapy of Longteng Tongluo Formula were skin itching,local redness,and swelling.The other adverse reactions with an

关 键 词：肺癌癌痛 龙藤通络方 阿片类止痛药 中医外治 UPLC-QQQ-MS/MS 

分 类 号：R273[医药卫生—中西医结合] R734.1[医药卫生—中医肿瘤科]