花宝金教授中西医结合治疗化疗敏感的小细胞肺癌的临床观察

发布时间：2018-05-14 01:17

本文选题：气机升降 + 队列研究　；参考：《北京中医药大学》2017年硕士论文

【摘要】：目的:观察花宝金教授运用中西医结合治疗化疗敏感的小细胞肺癌患者,对总生存期(Overall survival,OS)、无进展生存时间(progression-free survival,PFS)的影响,分析中医药在整体治疗过程中介入的合适时机,并对应用的方药进行讨论分析,为小细胞肺癌患者的治疗提供依据和帮助。方法:本研究采用探索性的队列研究模式,纳入2013年10月一2015年12月期间就诊于中国中医科学院广安门医院及中国医学科学院肿瘤医院的初治的门诊小细胞肺癌患者。根据是否接受中医药治疗为暴露因素,分为中西医结合队列和西医队列。研究总共纳入70例病例,脱落5例,最终完成治疗并纳入统计的共65例。其中,中西医结合队列组34例,包括局限期25例,广泛期9例;西医队列组31例,包括局限期20例,广泛期11例。西医队列采用EP/CE的一线化疗方案,治疗至少4-6周期,并结合患者实际情况施行放疗及预防性全脑放疗,中西医队列西医治疗同西医队列,中医治疗依据辨证要素不同及西医治疗阶段不同予以系列方药。气虚证:组方以黄芪、白术、茯苓、陈皮为基础加减;阴虚证:组方以北沙参、麦冬为基础加减;痰湿证:组方以瓜蒌、薤白、半夏为基础加减;血瘀证:组方以桃仁、赤芍、枳壳、桔梗、柴胡、川芎为基础加减;热毒证:组方以麻黄、生石膏、杏仁为基础加减。化疗阶段:多选用旋覆花、代赭石、半夏、黄连、熟地、山萸肉、阿胶、鹿角霜等中药辨证随症加减;放疗阶段:多选用瓜蒌、薤白、北沙参、麦冬、桔梗、荷梗、苏梗、麻黄、生石膏、杏仁等中药辨证随症加减;维持治疗阶段:多选用黄芪、白术、茯苓、陈皮、天麻、钩藤、石决明、酒大黄、姜黄、僵蚕、蝉蜕等中药辨证随症加减。4-6周期化疗后进入随访阶段。研究的主要终点指标包括OS、PFS、1年生存率、2年生存率、半年疾病无进展率、1年疾病无进展率、2年疾病无进展率;次要指标包括实体瘤疗效评价、中医症状评分改善情况、KPS评分变化情况以及NCI不良反应等。另外,本研究将中药介入的时机对PFS的影响纳入也列入观察,并对应用的方药进行讨论分析。结果:1生存分析:(1)中西医队列组与西医队列组的中位总生存期(Median Survival Time,MST)分别为24和20个月(P=0.221),1年、2年的累计生存率分别为94.1%、64.7%和80.6%、51.6%。经分层研究,局限期中西医队列组与西医队列组的MST分别为25和22个月(P=0.656),1年、2年的累计生存率分别为96.0%、48.0%和85.0%、35.0%;广泛期中西医队列组与西医队列组的MST分别为21和16个月(P=0.632),1年、2年的累计生存率分别为88.9%、22.2%和72.7%、18.2%。(2)中西医队列组与西医队列组的中位无进展生存时间(Median Progression Free Survival,mPFS)分别为19和14个月(P=0.098),半年、1年、2年无进展率分别为91.2%、70.6%、44.1%和74.2%、51.6%、29.0%。经分层研究,局限期中西医结合队列与西医队列比较,mPFS分别为19和15个月(P=0.421),半年无进展率分别为96.0%、85.0%,1年无进展率分别为80.0%、60.0%,2年无进展率分别为48.0%、35.0%;广泛期中西医结合队列与西医队列比较,mPFS分别为11和7个月(P=0.289),半年无进展率分别为77.8%、54.5%,1年无进展率分别为44.4%、36.4%,2年无进展率分别为33.3%、18.2%。(3)将中西医队列按照中药介入时间的不同分组,分为诊断后6个月以内介入中药组与超过6个月时间介入中药组。两组mPFS分别为24和19个月(P=0.809)。(4)以60岁为界,小于60岁与大于60岁的MST分别为25和21个月,差异具有统计学意义(P=0.002)。(5)按性别不同分组,男性和女性的MST分别为22和24个月(P=0.904)。(6)按KPS评分不同分组,KPS70分、80分、90分三组MST分别为12、22和25个月。KPS70分与80分相比,差异具有统计学意义(P=0.000);KPS70分与90分相比,差异具有统计学意义(P=0.001);KPS80分与90分相比,差异不具有统计学意义(P=0.492)。(7)按化疗方式不同分组,单纯化疗、序贯、夹心及同步放化疗的MST分别为20、22、24和32个月,单纯化疗与其他各组比较,差异均具有统计学意义(P值分别为0.038、0.042和0.026)。(8)按施行PCI的情况分组,施行PCI治疗与未行PCI治疗的MST分别为 32 和 20 个月(P=0.006)。2预后分析:进入Cox比例风险模型的预后因素分别是队列、年龄、KPS评分、PCI情况,Wald 值分别为 3.643、7.004、4.578、8.811,回归系数分别为-0.595、0.859、-1.320、-1.008,相对危险度分别为 0.551、2.361、0.267、0.365,P 值分别为 0.056、0.008、0.032、0.003。3实体瘤疗效:疗后42天、84天,两组的总有效率(Overall Response Rate,ORR)无统计学差异(P0.05),但在疗后126天,两组ORR相比P=0.052。疗后42天,两组的肿瘤疾病控制率(Disease Control Rate,DCR)无统计学差异(P0.05),但在疗后84天、126天,两组DCR具有统计学差异(P值分别为0.015和0.031)。4 KPS评分变化:疗后42天、84天、126天KPS评分变化情况,中西医队列和西医队列比较,差异均具有统计学意义(P0.05)。5中医临床症状疗效比较:对治疗前后中医临床症状疗效评价情况作比较,中西医队列组与西医队列组差异具有统计学意义(P=0.0l0),并对症状量表进行分析,结果发现在改善神疲乏力、气短、食欲不振、自汗盗汗、口干咽燥、胸闷、咳嗽、咯痰、便秘等9个症状方面,中西医队列与西医队列相比,差异具有统计学意义(P0.05)6 NCI不良反应分析:在血液系统不良反应方面,白细胞和血小板减少不良反应,两队列相比,差异不具有统计学意义(P0.05),在中性粒细胞及血红蛋白减少不良反应方面,两队列相比,差异具有统计学意义(P值分别为0.008和0.008);在消化系统不良反应各方面,两队列差异均不具有统计学意义(P0.05);在泌尿系统不良反应方面,肌酐不良反应,差异具有统计学意义(P=0.032)。7研究方药讨论分析:依据辨证要素不同及西医治疗阶段不同予以的系列方药,利用了药物的升降浮沉及性味归经,在疾病发展及西医治疗的不同阶段中针对用药,升清降浊,以使肺癌发生所涉脏腑顺应其各自的生理特性,气机升降恢复平衡,从而改善机体持续存在的恶性环境。结论:1初治的小细胞患者年龄不超过60岁、KPS评分高于70分,施行PCI治疗是影响小细胞肺癌生存的3个有益因素。2花宝金教授运用以气机升降为指导的中药治疗配合西医治疗较单纯西医治疗,可以改善化疗敏感的小细胞肺癌患者体力状况,缓解临床症状以及减轻血液系统和泌尿系统的不良反应。在延长OS、PFS方面有一定作用,并提示中药早期介入可能效果更佳,需扩大样本量以验证。
[Abstract]:Objective: To observe the effect of the combination of Chinese and Western Medicine on the treatment of chemotherapy sensitive small cell lung cancer patients with chemotherapy sensitive small cell lung cancer, the effect of Overall survival (OS) and progression-free survival, PFS). Methods: This study adopted an exploratory cohort study into the early treatment of small cell lung cancer patients in the Guanganmen Hospital of Chinese Academy of traditional Chinese medicine (Chinese Academy of Chinese Medicine) and the Cancer Hospital of the Chinese Academy of Medical Sciences in December 2015 October 2013. The exposure factors were divided into the combination of Chinese and Western medicine and the western medicine cohort. A total of 70 cases were included, 5 cases were dropped out, and the final treatment was completed in a total of 65 cases. Among them, 34 cases of integrated traditional Chinese and Western medicine group, including 25 cases of limited period, 9 cases extensively, 31 cases in the western medicine cohort, 20 cases in the inclusion Bureau, 11 in the extensive period, and EP/CE in the western medicine cohort. The first line chemotherapy regimen was treated at least 4-6 cycles, combined with the actual situation of the patients to carry out radiotherapy and preventive whole brain radiotherapy. Western medicine and Western medicine were used to treat the same Western medicine cohort. Traditional Chinese medicine treatment was based on different syndrome differentiation factors and different Western medicine treatment stages. Qi deficiency syndrome: the group was based on Astragalus, Atractylodes, Poria, and Pericarpium, and yin deficiency. Syndrome: the group with Radix Ophiopogon and Radix Ophiopogon as basic addition and subtraction, phlegm dampness syndrome: group with Trichosanthes, Allium scallion and Pinellia ternate; blood stasis syndrome: group with peach kernel, radix paeoniae rubra, Fructus aurantii, Radix Bupleuri, Ligusticum chuanxiong as basic addition and subtract; heat toxin syndrome: group with ephedra, gypsum and almond as the basis. The TCM syndrome differentiation and subtraction of Chinese herbal medicine, such as Cornus meat, Ejiao, antler frost, and other TCM syndrome differentiation, and radiotherapy stage: multiple selection of Trichosanthes, Allium macrostemon, Radix Ophiopogon, Rhizoma Ophiopogon, rhizome, ephedra, apricot kernel and other TCM syndrome differentiation and reduction; maintenance treatment stage: more selection of Astragalus, Atractylodes, tuckahoe, Chen peel, Gastrodia elata, rhubarb, rhubarb, turmeric, silkworm, cicada and other Chinese Medicine The main end points of the study were OS, PFS, 1 year survival rate, 2 year survival rate, six year disease progression rate, 1 year disease free progression rate, 1 year disease free progression rate, 2 year disease free progression rate, and secondary indexes including solid tumor evaluation, improvement of TCM symptom score, KPS score, and NCI did not. In addition, the effect of the timing of the intervention of traditional Chinese medicine on PFS was also included, and the application of the prescription was discussed and analyzed. Results: 1 Survival Analysis: (1) the median total survival period (Median Survival Time, MST) of the Chinese and Western medicine cohort group and the western medicine cohort were 24 and 20 months (P=0.221), 1 years, and 2 years' cumulative survival rate. Don't be 94.1%, 64.7%, and 80.6%. 51.6%. was studied by stratification. The MST of the traditional Chinese and Western medicine cohort and the western medicine cohort were 25 and 22 months (P=0.656), 1 years and 2 years were 96%, 48% and 85%, 35%, respectively. The extensive period of Chinese and Western Medicine cohort and the western medicine cohort were respectively 21 and 16 months (P=0.632), 1 years, and the cumulative birth years. The survival rates were 88.9%, 22.2% and 72.7% respectively. 18.2%. (2) the middle and Western medicine queue group and the western medicine queue group were 19 and 14 months (P=0.098), respectively, 19 and 14 months (P=0.098), half a year, 1 years, and 2 years, respectively, 91.2%, 70.6%, 44.1% and 74.2%, 51.6%, 29.0%. through stratified study, limited period and Western medicine team. Compared with the western medicine cohort, mPFS was 19 and 15 months (P=0.421) respectively. The non progress rate of half a year was 96%, 85%, and 1 year progression free rate was 80%, 60% and 35%, respectively, 48% and 35%, respectively. Compared with the western medicine cohort, mPFS was divided into 11 and 7 months (P=0.289), and the half year progression rate was 77.8%, respectively. The rate of no progress in 1 years was 44.4%, 36.4%, and 2 years, respectively, 33.3%. 18.2%. (3) divided the Chinese and Western medicine queues according to the different intervention time of Chinese medicine, divided into 6 months after the diagnosis and more than 6 months to intervene the traditional Chinese medicine group. The two group mPFS was 24 and 19 months (4) respectively. (4) with 60 years as the boundary, less than 60 and greater than those. MST was 25 and 21 months, respectively, and the difference was statistically significant (P=0.002). (5) according to gender differences, the MST of men and women were 22 and 24 months (P=0.904). (6) according to the KPS score, the differences were statistically significant (P=0.000), KPS70, 80, 90 and 25 months.KPS70 and 25 months respectively (P=0.000); KPS70 score. Compared with 90 points, the difference was statistically significant (P=0.001). Compared with 90 points, the difference was not statistically significant (P=0.492). (7) the differences were statistically significant (P value points) compared with other groups according to the different groups of chemotherapy, the MST of simple chemotherapy, sequential, sandwich and concurrent chemoradiotherapy were 20,22,24 and 32 months respectively. 0.038,0.042 and 0.026). (8) groups according to the implementation of PCI, the MST of the PCI treatment and the non PCI treatment was 32 and 20 months (P=0.006).2, respectively. The prognostic factors of the Cox proportional hazard model were the cohort, the age, the KPS score, the PCI, the Wald was 3.643,7.004,4.578,8.811, and the regression coefficients were respectively 95,0.859, -1.320, -1.008, relative risk was 0.551,2.361,0.267,0.365, P value was 0.056,0.008,0.032,0.003.3 solid tumor respectively: 42 days, 84 days after treatment, the total effective rate of two groups (Overall Response Rate, ORR) was not statistically significant (P0.05), but 126 days after the treatment, two groups of ORR compared with the two group of cancer control 42 days after treatment. Disease Control Rate (DCR) had no statistical difference (P0.05), but at 84 days and 126 days after treatment, the two groups of DCR had statistical difference (P value 0.015 and 0.031).4 KPS score changes: 42 days after treatment, 84 days, 126 days KPS score changes, the difference was statistically significant (P0.05).5 traditional Chinese medicine clinical symptoms (P0.05). Comparison of curative effect: the comparison of the clinical symptoms and symptoms of traditional Chinese medicine before and after treatment, the difference between the Chinese and Western medicine queue group and the western medicine queue group had statistical significance (P=0.0l0), and the symptom scale was analyzed. The results were found in the improvement of fatigue, shortness of breath, loss of appetite, sweating and sweating, dry mouth dryness, chest tightness, cough, phlegm, constipation, and other 9 symptoms. Compared with the western medicine cohort, the difference was statistically significant (P0.05) 6 NCI adverse reaction analysis: in the side effects of the blood system, leukocytes and thrombocytopenia decreased adverse reactions, and the differences were not statistically significant (P0.05). The two teams decreased the adverse reactions in neutrophils and hemoglobin. The difference was statistically significant (P value was 0.008 and 0.008), and the differences in the adverse reactions of the digestive system were not statistically significant (P0.05); the adverse reaction of the urinary system, the adverse reaction of the creatinine, was statistically significant (P=0.032) the analysis of the.7 research prescription: according to the differentiation of syndrome differentiation factors and the West A series of prescriptions which are different at the stage of medical treatment have made use of the rise and fall of the drugs and the sexual taste to the meridian. In the different stages of the disease development and the different stages of the western medicine treatment, the medicine should be raised to reduce the turbidity, so that the organs involved in the lung cancer should conform to their respective physiological characteristics, the Qi and the Qi can be restored and balanced, so as to improve the persistent malignant environment of the body. The age of 1 primary treatment of small cell patients is not more than 60 years old, KPS score is higher than 70. PCI treatment is the 3 beneficial factor affecting the survival of small cell lung cancer..2 Hua Bao Jin is treated with western medicine treatment in combination with western medicine, which is guided by the lifting of air machine, and can improve the physical condition of patients with chemotherapy sensitive small cell lung cancer. Alleviate the clinical symptoms and reduce the adverse reactions of the blood system and the urinary system. It has a certain role in prolonging the OS and PFS, and suggests that the early intervention of Chinese medicine may be better, and the sample size should be expanded to verify.

【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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