解毒颗粒治疗晚期肝癌的前瞻性队列研究及成本效果分析

发布时间：2018-03-05 19:23

本文选题：解毒颗粒　切入点：索拉非尼　出处：《第二军医大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景和目的原发性肝癌是临床上常见的恶性肿瘤之一,其中90%以上是肝细胞癌(以下简称肝癌),现已成为全球癌症相关死亡的第四大常见原因,是中国癌症死亡的第三大常见原因。肝细胞癌患者的结局较差,由于肝癌起病隐匿,因此肝细胞癌患者的结局较差,对目前现有的各种肿瘤治疗方式提出了极大的挑战。索拉非尼是唯一一种被美国肝病学会推荐的晚期肝癌药物,相对于安慰剂可以延长晚期肝癌患者的生存时间。但是,晚期肝癌患者服用索拉非尼的价格昂贵,毒性作用较大,生存获益极为有限,存在很多问题。而中药复方解毒颗粒在临床上运用多年,在治疗晚期肝癌中发挥了较好的作用。本研究旨在对比解毒颗粒和索拉非尼治疗晚期肝癌的有效性、安全性和经济学效益,分析影响疗效的相关因素。研究方法本研究采用前瞻性队列研究的方法,选取第二军医大学附属长海医院中医肿瘤科、第二军医大学附属长海医院介入科、第二军医大学附属东方肝胆外科医院中西医结合科、复旦大学附属中山医院中西医结合科、复旦大学附属肿瘤医院中西医结合科等科室在2013年10月至2016年12月接受解毒颗粒和索拉非尼治疗的晚期肝细胞癌患者作为研究对象,收集患者的年龄、性别、肝功能、肿瘤指标、手术资料、术后病理、药物不良反应等临床病理资料,随访至2017年2月。本研究主要终点指标是总生存时间,次要终点指标是无进展生存时间和安全性。同时,本研究通过构建Markov模型来进行成本效果分析,以增量成本效果比来作为成本效果分析的评价指标,并对影响结果的变量进行了敏感性分析。结果本研究共随访385例符合纳入标准的中晚期肝细胞癌患者,其中解毒颗粒组185人(55.93±11.15岁,男性85.4%),索拉非尼组162人(52.8±10.1岁,男性90.7%)。中位随访时间18.53个月(1-40个月)。解毒颗粒组的中位生存时间为6.7个月(95%CI:5.33-10.40),索拉非尼组的中位生存时间为8个月(95%CI:7.27-10.53),P值为0.402,两者差异没有统计学意义(P0.05)。解毒颗粒组的中位无进展生存时间为3.22个月(95%CI:2.97-3.70),索拉非尼组的中位无进展生存时间为3.57个月(95%CI:2.77-4.03),P值为0.442,两者差异没有统计学意义(P0.05)。COX回归多因素分析发现,ECOG评分、最大肿瘤直径和、丙氨酸氨基转氨酶、天门冬氨酸氨基转移酶、甲胎蛋白是最主要的生存时间预测因素。CHILD分级、ECOG评分、腹水情况、天门冬氨酸氨基转移酶、甲胎蛋白是最主要的无进展生存时间预测因素。索拉非尼组的患者出现了腹泻、手足综合症等不良反应,其中,腹泻的发生率远高于解毒颗粒组。本研究采用倾向性评分匹配的方法来减少两组间的不均衡,两组共155对匹配成功。解毒颗粒组的中位生存时间为8.6个月(95%CI:5.60-10.77),索拉非尼组的中位生存时间为8个月(95%CI:7.26-10.53),P值为0.534,两者差异没有统计学意义(P0.05)。解毒颗粒组的中位无进展生存时间为3.23个月(95%CI:2.97-3.80),索拉非尼组的中位无进展生存时间为3.60个月(95%CI:2.77-4.20),P值为0.686,两者差异没有统计学意义(P0.05)。COX回归多因素分析发现,ECOG评分、最大肿瘤直径和、丙氨酸氨基转氨酶、天门冬氨酸氨基转移酶、甲胎蛋白是最主要的生存时间预测因素。CHILD分级、ECOG评分、腹水情况、天门冬氨酸氨基转移酶、甲胎蛋白是最主要的无进展生存时间预测因素。研究结果和匹配之前的结果保持一致。成本效果分析显示,解毒颗粒组患者获得的质量调整生命年为0.34年,费用为32122.584元,索拉非尼组患者获得的质量调整生命年为0.42年,费用为266864.155元,索拉非尼组相对于解毒颗粒组的增量成本效果比为635390.845元。经过敏感度分析后结果保持一致,索拉非尼组稳定期的费用、稳定期的效应值、解毒颗粒组稳定期的费用是对模型敏感度影响最大的因素。结论1、解毒颗粒和索拉非尼治疗晚期肝癌患者的生存时间和无进展生存时间之间没有显著的统计学差异。2、解毒颗粒治相比于索拉非尼,具有更好的安全性和经济学效益。
[Abstract]:Background and objective: primary hepatocellular carcinoma is one of the most common malignant tumors, of which more than 90% of hepatocellular carcinoma (HCC), has now become the fourth most common cause of cancer-related death worldwide, is the third most common cause of cancer death. China hepatocellular carcinoma patients with poor outcome, because of insidious onset of liver cancer therefore, the poor outcome in patients with hepatocellular carcinoma, which is a great challenge for the existing tumor treatment. Sorafenib is the only one by AASLD recommended advanced liver cancer drugs, compared with placebo can prolong the survival time of patients with advanced liver cancer. However, patients with advanced liver cancer taking Sola Fini's expensive, toxic effect a large, survival benefit is very limited, there are a lot of problems. And the traditional Chinese medicine compound Jiedu Granule using in clinic for many years, in the treatment of advanced hepatocellular carcinoma play a better The role of the effectiveness. The purpose of this study is to contrast and Sola Fini Jiedu Granule in the treatment of advanced liver cancer, safety and economic benefit, analyze the related factors affecting the efficacy. Methods: This study adopts method of prospective cohort studies, selection of Chinese Medicine Department of Tumor Hospital of Second Military Medical University affiliated Changhai Affiliated Hospital of Second Military Medical University, Department of Radiology, Department of Second Military Medical University Oriental Department of Hepatobiliary Surgery Hospital of traditional Chinese medicine and Western medicine, Zhongshan Hospital Affiliated to Fudan University, Tumour Hospital Affiliated to Fudan University, Department of integrated traditional Chinese and Western medicine, integrative medicine and other departments from October 2013 to December 2016 and Sola Fini accept Jiedu Granule in the treatment of advanced hepatocellular carcinoma patients as the research object, collect the patient's age, gender, liver function, tumor markers, operative procedures, postoperative pathology, clinical and pathological data of adverse drug the reaction, this study followed until February 2017. The primary end point was survival, a secondary end point is no time and safety in existence. At the same time, this study builds the Markov model for cost effectiveness analysis, with the incremental cost effectiveness ratio as evaluation index of cost effectiveness analysis, and on the variable sensitivity analysis is carried out. The results of this study were followed up for 385 patients met the inclusion criteria in patients with advanced hepatocellular carcinoma, which Jiedu Granule group 185 (55.93 + 11.15 years, 85.4% male), sorafenib group 162 (52.8 + 10.1 years, 90.7% male). The median follow-up time was 18.53 months (1-40 months). The median survival time of Jiedu Granule group for 6.7 months (95%CI:5.33-10.40), the median survival time of sorafenib group was 8 months (95%CI:7.27-10.53), P value was 0.402, the difference was not statistically significant (P0.05). Jiedu Granule groups of median progression free survival time was 3.22 April (95%CI:2.97-3.70), sorafenib group the median progression free survival time was 3.57 months (95%CI:2.77-4.03), P value was 0.442, the difference was not statistically significant (P0.05) and multiple.COX regression analysis showed that ECOG score, maximum tumor diameter, alanine aminotransferase, aspartate aminotransferase, AFP protein is the most important predictor of survival time of.CHILD grade, ECOG score, ascites, aspartate aminotransferase, alpha fetoprotein is progression free survival time prediction of the main factors. The sorafenib group patients experienced diarrhea, adverse reactions, hand foot syndrome, the incidence of diarrhea than detoxification particle group. This study used propensity score matching method to reduce the imbalance between the two groups, two groups of 155 to match the success. The median survival time of Jiedu Granule group was 8.6 months (95%CI:5.60-10.77), Sora The median survival time of sorafenib group was 8 months (95%CI:7.26-10.53), P value was 0.534, the difference was not statistically significant (P0.05). Jiedu Granule group median progression free survival time was 3.23 months (95%CI:2.97-3.80), sorafenib group the median progression free survival time was 3.60 months (95%CI:2.77-4.20) and the P value is 0.686, the difference was not statistically significant (P0.05) and multiple.COX regression analysis showed that ECOG score, maximum tumor diameter, alanine aminotransferase, aspartate aminotransferase, alpha fetoprotein is a predictor of.CHILD grade, time deposit the main ECOG score, ascites, aspartic acid aminotransferase, AFP is progression free survival time prediction of the main factors. The research results and results before matching is consistent. Cost effectiveness analysis showed that the obtained Jiedu Granule group were 0. quality adjusted life years For 34 years, at a cost of 32122.584 yuan, get the sorafenib group with quality adjusted life years for 0.42 years, at a cost of 266864.155 yuan, sorafenib group compared to the incremental cost effectiveness ratio in group Jiedu Granule was 635390.845 yuan. After the sensitivity analysis results are consistent, sorafenib group of stable cost, stable effect the value of group Jiedu Granule stable period cost is the largest influence on the model sensitivity factors. The conclusion of the 1, and Sola Fini Jiedu Granule in treatment of advanced liver cancer patient survival and progression free survival time between no significant statistical difference between the.2 treatment compared to Sola Fini Jiedu Granule, has better safety and economic benefits.

【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

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