本文選題：解毒顆粒　切入點(diǎn)：索拉非尼　出處：《第二軍醫(yī)大學(xué)》2017年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：背景和目的原發(fā)性肝癌是臨床上常見(jiàn)的惡性腫瘤之一,其中90%以上是肝細(xì)胞癌(以下簡(jiǎn)稱(chēng)肝癌),現(xiàn)已成為全球癌癥相關(guān)死亡的第四大常見(jiàn)原因,是中國(guó)癌癥死亡的第三大常見(jiàn)原因。肝細(xì)胞癌患者的結(jié)局較差,由于肝癌起病隱匿,因此肝細(xì)胞癌患者的結(jié)局較差,對(duì)目前現(xiàn)有的各種腫瘤治療方式提出了極大的挑戰(zhàn)。索拉非尼是唯一一種被美國(guó)肝病學(xué)會(huì)推薦的晚期肝癌藥物,相對(duì)于安慰劑可以延長(zhǎng)晚期肝癌患者的生存時(shí)間。但是,晚期肝癌患者服用索拉非尼的價(jià)格昂貴,毒性作用較大,生存獲益極為有限,存在很多問(wèn)題。而中藥復(fù)方解毒顆粒在臨床上運(yùn)用多年,在治療晚期肝癌中發(fā)揮了較好的作用。本研究旨在對(duì)比解毒顆粒和索拉非尼治療晚期肝癌的有效性、安全性和經(jīng)濟(jì)學(xué)效益,分析影響療效的相關(guān)因素。研究方法本研究采用前瞻性隊(duì)列研究的方法,選取第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院中醫(yī)腫瘤科、第二軍醫(yī)大學(xué)附屬長(zhǎng)海醫(yī)院介入科、第二軍醫(yī)大學(xué)附屬東方肝膽外科醫(yī)院中西醫(yī)結(jié)合科、復(fù)旦大學(xué)附屬中山醫(yī)院中西醫(yī)結(jié)合科、復(fù)旦大學(xué)附屬腫瘤醫(yī)院中西醫(yī)結(jié)合科等科室在2013年10月至2016年12月接受解毒顆粒和索拉非尼治療的晚期肝細(xì)胞癌患者作為研究對(duì)象,收集患者的年齡、性別、肝功能、腫瘤指標(biāo)、手術(shù)資料、術(shù)后病理、藥物不良反應(yīng)等臨床病理資料,隨訪至2017年2月。本研究主要終點(diǎn)指標(biāo)是總生存時(shí)間,次要終點(diǎn)指標(biāo)是無(wú)進(jìn)展生存時(shí)間和安全性。同時(shí),本研究通過(guò)構(gòu)建Markov模型來(lái)進(jìn)行成本效果分析,以增量成本效果比來(lái)作為成本效果分析的評(píng)價(jià)指標(biāo),并對(duì)影響結(jié)果的變量進(jìn)行了敏感性分析。結(jié)果本研究共隨訪385例符合納入標(biāo)準(zhǔn)的中晚期肝細(xì)胞癌患者,其中解毒顆粒組185人(55.93±11.15歲,男性85.4%),索拉非尼組162人(52.8±10.1歲,男性90.7%)。中位隨訪時(shí)間18.53個(gè)月(1-40個(gè)月)。解毒顆粒組的中位生存時(shí)間為6.7個(gè)月(95%CI:5.33-10.40),索拉非尼組的中位生存時(shí)間為8個(gè)月(95%CI:7.27-10.53),P值為0.402,兩者差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P0.05)。解毒顆粒組的中位無(wú)進(jìn)展生存時(shí)間為3.22個(gè)月(95%CI:2.97-3.70),索拉非尼組的中位無(wú)進(jìn)展生存時(shí)間為3.57個(gè)月(95%CI:2.77-4.03),P值為0.442,兩者差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P0.05)。COX回歸多因素分析發(fā)現(xiàn),ECOG評(píng)分、最大腫瘤直徑和、丙氨酸氨基轉(zhuǎn)氨酶、天門(mén)冬氨酸氨基轉(zhuǎn)移酶、甲胎蛋白是最主要的生存時(shí)間預(yù)測(cè)因素。CHILD分級(jí)、ECOG評(píng)分、腹水情況、天門(mén)冬氨酸氨基轉(zhuǎn)移酶、甲胎蛋白是最主要的無(wú)進(jìn)展生存時(shí)間預(yù)測(cè)因素。索拉非尼組的患者出現(xiàn)了腹瀉、手足綜合癥等不良反應(yīng),其中,腹瀉的發(fā)生率遠(yuǎn)高于解毒顆粒組。本研究采用傾向性評(píng)分匹配的方法來(lái)減少兩組間的不均衡,兩組共155對(duì)匹配成功。解毒顆粒組的中位生存時(shí)間為8.6個(gè)月(95%CI:5.60-10.77),索拉非尼組的中位生存時(shí)間為8個(gè)月(95%CI:7.26-10.53),P值為0.534,兩者差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P0.05)。解毒顆粒組的中位無(wú)進(jìn)展生存時(shí)間為3.23個(gè)月(95%CI:2.97-3.80),索拉非尼組的中位無(wú)進(jìn)展生存時(shí)間為3.60個(gè)月(95%CI:2.77-4.20),P值為0.686,兩者差異沒(méi)有統(tǒng)計(jì)學(xué)意義(P0.05)。COX回歸多因素分析發(fā)現(xiàn),ECOG評(píng)分、最大腫瘤直徑和、丙氨酸氨基轉(zhuǎn)氨酶、天門(mén)冬氨酸氨基轉(zhuǎn)移酶、甲胎蛋白是最主要的生存時(shí)間預(yù)測(cè)因素。CHILD分級(jí)、ECOG評(píng)分、腹水情況、天門(mén)冬氨酸氨基轉(zhuǎn)移酶、甲胎蛋白是最主要的無(wú)進(jìn)展生存時(shí)間預(yù)測(cè)因素。研究結(jié)果和匹配之前的結(jié)果保持一致。成本效果分析顯示,解毒顆粒組患者獲得的質(zhì)量調(diào)整生命年為0.34年,費(fèi)用為32122.584元,索拉非尼組患者獲得的質(zhì)量調(diào)整生命年為0.42年,費(fèi)用為266864.155元,索拉非尼組相對(duì)于解毒顆粒組的增量成本效果比為635390.845元。經(jīng)過(guò)敏感度分析后結(jié)果保持一致,索拉非尼組穩(wěn)定期的費(fèi)用、穩(wěn)定期的效應(yīng)值、解毒顆粒組穩(wěn)定期的費(fèi)用是對(duì)模型敏感度影響最大的因素。結(jié)論1、解毒顆粒和索拉非尼治療晚期肝癌患者的生存時(shí)間和無(wú)進(jìn)展生存時(shí)間之間沒(méi)有顯著的統(tǒng)計(jì)學(xué)差異。2、解毒顆粒治相比于索拉非尼,具有更好的安全性和經(jīng)濟(jì)學(xué)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.

【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735.7

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