中医药综合方案联合化疗治疗晚期非小细胞肺癌的随机对照研究

发布时间：2018-04-26 06:34

本文选题：安全性 + 非小细胞肺癌　；参考：《北京中医药大学》2017年硕士论文

【摘要】：近年来,非小细胞肺癌的发病率和死亡率不断上升,由于半数以上患者在首次诊断时已经发生了远处转移或无法手术治疗,化疗成为了目前晚期非小细胞肺癌治疗的重要手段之一。但化疗往往带来的不良反应如骨髓抑制、消化道反应、癌性疲乏等也成为了严重影响非小细胞肺癌患者生活质量和治疗选择的重要因素,而目前以对症支持治疗为主的减毒疗效尚不能令人满意。如何进一步提高晚期非小细胞肺癌化疗疗效、减轻毒副反应和提高生活质量已成为现代医学亟待解决的问题。中医药治疗与化疗协同在晚期非小细胞肺癌治疗中发挥着增效减毒、提高患者生活质量等重要作用。广安门医院肿瘤科前期承担了多项科技攻关计划课题,整合优化全国的优势力量,制订了中医治疗肺癌的综合治疗方案,即《肺癌中医临床指引》。根据《指引》推荐中医综合方案与化疗的联合治疗在提高化疗完成率及疗效、改善症状、提高生存质量均具有独特的优势,但国内外临床研究尚缺乏。目的:验证中医综合方案联合晚期非小细胞肺癌化疗增效减毒效果,评估中医综合方案在联合化疗治疗阶段的安全性。方法:本研究通过多中心、前瞻性随机对照设计,纳入晚期非小细胞肺癌患者360例,随机分为治疗组182例,对照组178例。治疗组采用NCCN指南标准化学治疗联合以健脾和胃、益气养血、滋补肝肾为主要原则的中医综合方案,对照组接受单纯NCCN指南标准化疗或联合使用汤药但仅可采用二陈汤加减化裁。化疗21-28天为一周期,连续治疗2个周期后,评估疗效。治疗应达到2个周期,完成者为完整病例,未能完成者只做安全性评价。使用国际公认的评效方式:实体瘤的疗效评价标准(RECIST1.1标准评价)、常见不良反应事件评价标准(NCI-CTCAE3.0)、《中药新药临床指导原则》中肺癌中医临床证候积分评价标准、美国肺癌生存质量量表(FACT-L4.0版))对化疗完成率、瘤体缓解、稳定情况、肿瘤标志物变化、不良反应情况、中医临床证候、生活质量情况进行评效。采用SPSS20.0进行统计分析。结果:共纳入360例非小细胞肺癌患者,共完成315例,治疗组163例,对照组150例,两组患者在性别、年龄、病理类型、肿瘤分期、体力状况、生命体征、治疗前实体瘤大小、肿瘤标志物水平(CEA、SCC、CyFRA211)、中医证候、生活质量各领域积分等方面基线水平均无统计学差异(P0.05),患者疾病基线特征方面,两组间具有可比性。增效指标:1、化疗完成率:两组完成率相近,未显示明显差异(P0.05);2、实体瘤疗效:两组客观缓解率(ORR=CR+PR)相近:治疗组有效率13.2%,对照组有效率13.5%,未显示明显差异(P0.05)。临床获益率(CBR=CR+PR+SD)治疗组为64.8%略优于对照组的62.9%,但两组间无统计学差异(P0.05);3、肿瘤标志物变化评价:2疗后治疗组CEA水平低于对照组,存在统计学差异(P0.05);SCC及CyFRA211两组间无统计学差异(P0.05)。CEA、SCC、CyFRA211指标较基线变化均显示良好的趋势,但两组间无统计学差异(P0.05)。说明中医综合治疗在提高化疗完成率、肿瘤控制率和降低肿瘤标志物水平上具有一定趋势,但增效效果不著。减毒指标:1、化疗毒副反应:NCI不良反应评价显示治疗组在血液系统毒性白细胞一项中明显优于对照组,存在统计学差异(P0.05);临床症状部分治疗组在疲劳(嗜睡、不适、乏力)、食欲下降、恶心、呕吐4项中明显优于对照组,可见统计学差异(P0.05);2、中医证候评价:2疗程后症状积分总和两组间无统计学差异;但治疗组积分总和较基线变化情况优于对照组,存在统计学差异(P0.05);参照《中药新药临床研究指导原则》中肺癌中医临床证候计分评价标准评定,治疗组总有效率45.1%高于对照组总有效率29.2%,具有统计学差异(P0.05);单项条目对比中治疗组在神疲乏力、胸闷2项中明显优于对照组,具有统计学差异(P0.05);3、生存质量评价:2疗程后治疗组PWB(生理状况)、EWB(情感状况)优于对照组,存在统计学差异(P0.05);单项条目对比中治疗组在精力不济、感到恶心、在与疾病抗争中感到越来越失望、担心可能会死、担心病情会恶化、能够面对疾病、食欲好等条目优于对照组,具有统计学差异(P0.05)。说明中医综合治疗在降低化疗毒副反应、改善中医证候、提高生活质量上均具有显著优势。安全性评价:研究中除NCI不良反应量表记录的不良反应外,治疗组出现不良事件1例(0.5%),对照组出现不良事件1例(0.6%),判断与试验药物无关。无其他不良反应记录。说明中医综合治疗方案安全性良好,适于临床推广。结论:中医综合治疗在提高化疗完成率、肿瘤控制率和降低肿瘤标志物水平上具有一定作用趋势,但增效效果不显著;中医综合治疗在降低化疗毒副反应、改善中医证候、提高生活质量上均具有显著优势。中医综合治疗安全性良好,适于临床推广。
[Abstract]:In recent years, the incidence and mortality rate of non-small cell lung cancer are increasing, because more than half of the patients have undergone distant metastasis or inoperable treatment at the first diagnosis. Chemotherapy has become one of the most important methods for the treatment of advanced non-small cell lung cancer, but chemotherapy often brings adverse reactions such as bone marrow suppression and digestive tract reactions. Cancer fatigue has also become an important factor affecting the quality of life and the choice of treatment for patients with non-small cell lung cancer. However, the effect of reducing toxicity mainly on symptomatic support is not satisfactory. How to further improve the therapeutic effect of advanced non-small cell lung cancer, reduce the side effects and improve the quality of life has become a modern medicine. In the treatment of advanced non-small cell lung cancer, the cooperation of traditional Chinese medicine and chemotherapy in the treatment of advanced non-small cell lung cancer is playing an important role in improving the quality of life and so on. In the early stage of the Department of oncology in Guanganmen hospital, a number of scientific and technological projects have been undertaken to integrate and optimize the national superior forces, and a comprehensive therapeutic prescription for the treatment of lung cancer in traditional Chinese medicine has been formulated. According to the guideline > the combined treatment of TCM and chemotherapy has unique advantages in improving the completion rate of chemotherapy, improving the curative effect, improving the symptoms and improving the quality of life. However, the clinical research at home and abroad is still lacking. Effect, evaluate the safety of TCM Comprehensive Scheme in the stage of combined chemotherapy. Methods: through multi center, prospective randomized controlled design, 360 patients with advanced non-small cell lung cancer were randomly divided into treatment group (182 cases) and control group (178 cases). The treatment group was treated with NCCN guide standard chemical therapy combined with spleen and stomach, nourishing qi and blood nourishing, nourishing blood. The main principle of supplementing the liver and kidney is the comprehensive plan of traditional Chinese medicine. The control group receives only NCCN guide standard chemotherapy or combined use of decoction but can only use the decoction of second Chen decoction. 21-28 days of chemotherapy is a cycle, after 2 cycles of continuous treatment, the curative effect is evaluated. The treatment should reach 2 cycles, the complete case is complete, and the failure to complete the safety assessment only. Price. Using the internationally recognized evaluation methods: the evaluation standard of the curative effect of solid tumor (RECIST1.1 standard evaluation), the standard of evaluation of common adverse events (NCI-CTCAE3.0), the evaluation standard of the TCM clinical syndromes of lung cancer in the clinical guiding principle of the new medicine, the American Lung Cancer Quality of Life Scale (FACT-L4.0 version), the rate of chemotherapy and the remission of the tumor, The stability, the change of tumor markers, the adverse reaction, the TCM clinical syndrome and the quality of life were evaluated by SPSS20.0. Results: a total of 360 patients with non-small cell lung cancer were included in 315 cases, 163 cases in the treatment group and 150 cases in the control group. The two groups were in sex, age, pathological type, tumor staging and physical condition. The vital signs, the size of the solid tumor before treatment, the level of the tumor markers (CEA, SCC, CyFRA211), the TCM syndromes and the integration of the quality of life were not statistically different (P0.05). The baseline features of the patients were comparable between the two groups. The increase efficiency index: 1, the completion rate of chemotherapy: the two groups had similar completion rates, and did not show significant differences. (P0.05); 2, the effect of solid tumor: two groups of objective remission rate (ORR=CR+PR) similar: the treatment group was effective 13.2%, the control group was 13.5%, no significant difference (P0.05). The clinical benefit rate (CBR=CR+PR+SD) treatment group was 64.8% slightly better than the control group, but there was no statistical difference between the two groups (P0.05); 3, the tumor marker change evaluation: 2 treatment group after the treatment group. The level of CEA was lower than that of the control group (P0.05); there was no statistical difference between the two groups (P0.05).CEA, SCC, and CyFRA211 index showed a good trend compared with the baseline, but there was no statistical difference between the two groups (P0.05). It indicated that the comprehensive treatment of TCM was in the high chemotherapy completion rate, the tumor control rate and the level of tumor markers. There was a certain trend, but the effect was not effective. The detoxification index: 1, the side effects of chemotherapy: the NCI adverse reaction evaluation showed that the treatment group was obviously superior to the control group in the blood system toxic leukocyte, and there was a statistical difference (P0.05); the clinical symptom group was in fatigue (lethargy, discomfort, fatigue), appetite decline, nausea and vomiting. Significantly better than the control group, there was statistical difference (P0.05); 2, TCM Syndrome Evaluation: after the 2 course of treatment, there was no statistical difference between the two groups, but the total score of the treatment group was better than the baseline, and there was a statistical difference (P0.05). Standard evaluation, the total effective rate of the treatment group was 45.1% higher than the control group, the total effective rate was 29.2%, with statistical difference (P0.05). In the single item comparison, the treatment group was obviously superior to the control group in the fatigue and chest tightness in 2 items, with statistical difference (P0.05); 3, the quality of life evaluation: the 2 course of treatment group PWB (physiological condition), EWB (emotional state) is superior to the control Group, there was a statistical difference (P0.05); in the comparison of the single item, the treatment group was disappointing, felt more disappointing in the fight against the disease, worried that it might die, worried that the condition would deteriorate, and could face the disease, and the appetite was better than the control group, with statistical difference (P0.05). In the study, there were 1 cases of adverse events (0.5%) in the treatment group and 1 cases (0.6%) of adverse events in the control group. No other adverse reaction records were recorded. There was no other adverse reaction record. The treatment scheme is safe and suitable for clinical popularization. Conclusion: TCM Comprehensive treatment has a certain role in improving the completion rate of chemotherapy, the rate of tumor control and reducing the level of tumor markers, but the effect is not significant. The comprehensive treatment of traditional Chinese medicine has significant advantages in reducing the side effects of chemotherapy, improving TCM syndromes and improving the quality of life. Comprehensive treatment of Chinese medicine is safe and suitable for clinical promotion.

【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

【参考文献】