吉非替尼(易瑞沙)用药手册

中国易瑞沙扩大用药项目中晚期非小细胞肺癌长期生存患者的研究李龙芸;蒋国梁;徐建明;陈嘉;陶敏;罗荣城;李为民;徐农;赵肖;王孟昭;钟巍;廖美琳;陈黎;韩宝惠;管忠震;于世英;刘叙仪;吴一龙【摘要】背景与目的中国易瑞沙(吉非替尼、ZD1839)扩大用药(EAP)项目开始于2001年,旨在为标准治疗失败后或不能耐受化疗的晚期非小细胞肺癌( non-small cell lung cancer,NSCLC)患者提供吉非替尼单药治疗.本研究主要评估仍在EAP长期生存者的生活质量、肿瘤控制情况、服药安全性、临床特点及基因测定.次要目标为探讨长期生存者的临床特征.方法这是一项描述性观察研究,数据收集依据流行病学研究方法.对于仍在EAP组中的患者,数据将采用横断面调查的方法;对于已从EAP组中退出的长期生存者和快速进展者,数据以回顾性方式收集.结果在EAP数据库中共筛选出符合条件的患者934例,其中59例例服用吉非替尼＞3年的长期生存者,包括25例仍在EAP组,34例已退出EAP组,875例为快速进展者.59例长期生存者来自中国国15个临床中心.仍在EAP组的长期生存者,中位肺癌治疗功能评价量表(functional assessment of cancer therapy-lung,FACT-L)、试验结果系数( trial outcome index,TOI)和肺癌量表(lung cancer subscale,LCS)分值分别为64.5、37和12.5,91.6％患者的体力状态( performance status,PS)为0分-1分,客观有效率、疾病控制率和中位有效持续时间分别为37.5％、87.5％和168个月.在59例长期生存者中,没有发现严重或新的不良反应;其中＜65岁者68.5％,腺癌81.4％,女性55.9％,从不吸烟者71％.与快速进展并比较,长期生存者中女性比例稍高(P=0.02).本研究收集了3例患者的组织标本,其中1例EGFR突变阳性;2例Ki-67蛋白表达阳性,这2例患者生存期都超过73个月.同时收集了22例血浆标本,1例EGFR突变阳性.结论部分晚期NSCLC 应用吉非替尼治疗可获3年以上长期生存,并为长期生存者提供了良好的生活质量、满意的疗效和药物耐受性.%Background and objective The Expand Access Program(EAP)oflressa(gefitinib, ZD1839) in China was initiated in 2001 with the aim of providing gefitinib to non-small cell lung cancer (NSCLC) patients who failed to respond to standard treatment or who could not tolerate chemotherapy. The primary objective was to describe the quality of life (QpL), tumor control status, drug safety, and clinical/genomic features of active long-term survivors enrolled in the EAP. The secondary objective was to determine the clinical characteristics of long-term survivors in the EAP program. Methods In this descriptive observational study, data were collected based on epidemiological research methods. The data of patients who were actively participating in the EAP and still undergoing gefitinib treatment were collected in a cross-sectional manner to reflect the current status of each patient Meanwhile, the data of patients who had been on ge6tinib treatment for more than three years and had already been terminated from the EAP or those who were fast progressors were collected retrospectively. Results A total of 934 patients were screened in the EAP database. Among these patients, 25 were active long-term survivors stili enrolled in the EAP and 34 were long-term survivors who had been terminated from the program. These 59 patients were enrolled in IS different centers in China, and the remaining 87S patients were fast progressors. The median scores for the Functional Assessment of Cancer Therapy-Lung (FACT-L), Trial Outcome Index (TOI), and Lung Cancer Subscale (LCS) of the 25 long-term survivors were 64.5, 37 and 12.5,respectively. The performance status 0-1 accounted for 91.6% of the data observed during the cross-sectional survey. For active long-term survivors, the objective response rate was 37.5%, the disease control rate was 87.5%, and the median duration of response time was almost 68 months. In the long-term survivor group, no serious and new adverse events were reported. Patients who were aged under 65 years (68.5%), affected with adenocarcinoma (81.4%), female (55.9%), or had never smoked (71%) accounted for majority of the long-term survivors. The percentage of females was significantly higher in the long-term survivor group than in the fast progressor group (P=0.02). Three tissue samples were collected from each of the 24 active long-term survivors, and one patient was found to be positive o(FR mutation. Twenty-two blood samples were also collected, and one patient tested positive for EGFR mutation. The Ki67 protein expression was also tested in three tissue samples, and two of these were found positive for Ki67 protein expression, with a response duration time of over 73 months. Conclusion A 250 mg dose of gefitinib offers good QpL and is safe for advanced NSCLC long-term survivors even after more than three years of treatment. According to the evaluation of the current tumor control statuses of patients, gefitinib demonstrates good efficacy in these active long-term survivors.【期刊名称】《中国肺癌杂志》【年(卷),期】2012(015)006【总页数】8页(P332-339)【关键词】肺肿瘤;吉非替尼;中国易瑞沙扩大用药;长期生存【作者】李龙芸;蒋国梁;徐建明;陈嘉;陶敏;罗荣城;李为民;徐农;赵肖;王孟昭;钟巍;廖美琳;陈黎;韩宝惠;管忠震;于世英;刘叙仪;吴一龙【作者单位】100730北京,中国医学科学院北京协和医学院北京协和医院;200032上海,复旦大学附属肿瘤医院;100071北京,中国人民解放军307医院;210009南京,江苏省肿瘤医院;215006苏州,苏州大学第一附属医院;510515广州,南方医院;610041成都,四川大学华西医院;310003杭州,浙江大学医学院附属第一医院;100730北京,中国医学科学院北京协和医学院北京协和医院;100730北京,中国医学科学院北京协和医学院北京协和医院;100730北京,中国医学科学院北京协和医学院北京协和医院;200030上海,上海交通大学附属胸科医院;250117济南,山东省肿瘤医院;200030上海,上海交通大学附属胸科医院;510060广州,中山大学附属肿瘤医院;430030武汉,华中科技大学同济医学院附属同济医院;100142北京,北京肿瘤医院;510080广州,广东省人民医院【正文语种】中文【中图分类】R734.2易瑞沙（吉非替尼、ZD1839）扩大用药项目（Expand Access Program, EAP 1839IL/0052）于2001年-2007年在中国进行，旨在为标准治疗失败、无法接受其它系统性抗肿瘤治疗、无法耐受化疗、或因无法或不适用其它吉非替尼临床研究的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者提供吉非替尼单药治疗，入选该项目患者约1,600例。

吉非替尼的生产工艺设计.目录一、目标化合物的概述1二、目标化合物已有合成路线简介2三、目标化合物已有合成路线优劣分析7四、目标化合物新合成路线设计9五、吉非替尼步骤工艺流程设计及工艺流程操作简述10六、总结13参考文献14word教育资料一目标化合物的概述 1. 简介吉非替尼(Gefitinib)，又名易瑞沙(Iressa)是由AstraZneneca公司开发的一种新型抗肿瘤药物，它是针对EGFR蛋白酪氨酸激酶的口服小分子抑制剂。

易瑞沙(zDl839)分子在1994年被发现，在后来的一些列研究中发现，h'essa分子可以抑制头颈部癌、直肠癌、前列腺癌、乳腺癌等NSCLC细胞的生长及存活。

XXXX年经日本厚生省批准在日本首次上市，用于治疗不可手术或者转移复发的非小细胞肺癌。

吉非替尼在美国及澳大利亚被获准上市的时间是XXXX年5月，作为三线单一治疗晚期NSCLC药物，它是第一个用于实体瘤治疗的小分子蛋白酪氨酸激酶抑制类抗癌药物。

XXXX年中国抗癌协会肺癌专业委员会对不能手术的NSCLC 的治疗指引中提出：Iressa推荐用于治疗局部晚期或远处转移的非小细胞肺癌含铂类方案及Docetaxel化疗失败的病人。

XXXX年2月25日经国家食品药品监督管理局(SFDA)正式批准在中国上市(商品通用名：吉非替尼)，用于治疗已经接受过化学治疗或者不能接受化疗的局部晚期非小细胞肺癌或者转移性非小细胞肺癌。

2. 理化性质吉非替尼的化学名是：4-一、目标化合物的概述1二、目标化合物已有合成路线简介2三、目标化合物已有合成路线优劣分析7四、目标化合物新合成路线设计9五、吉非替尼步骤工艺流程设计及工艺流程操作简述10六、总结13参考文献14word教育资料一目标化合物的概述 1. 简介吉非替尼(Gefitinib)，又名易瑞沙(Iressa)是由AstraZneneca公司开发的一种新型抗肿瘤药物，它是针对EGFR蛋白酪氨酸激酶的口服小分子抑制剂。