老年中晚期非小细胞肺癌化疗与华蟾素治疗的对比研究

目录一、摘要……………………………………………………………1（一）中文摘要…………………………………………………1（二）英文摘要…………………………………………………3二、文献综述………………………………………………………6（一）综述………………………………………………………6（二）参考文献…………………………………………………13三、正文…………………………………………………………16（一）前言………………………………………………………16（二）材料和方法………………………………………………16（三）结果………………………………………………………18（四）讨论………………………………………………………22（五）结论………………………………………………………28（六）参考文献…………………………………………………291老年中晚期非小细胞肺癌化疗与华蟾素治疗的对比研究硕士生姓名：朱琳指导教师：崔晓楠教授专业名称：肿瘤学摘要目的：肺癌是恶性肿瘤的主要死亡原因，在我国肺癌发病率及死亡率均成上升趋势，其中80%是非小细胞肺癌。大多数非小细胞肺癌患者发现时多属晚期，失去手术治疗的机会，在晚期非小细胞肺癌的全身治疗中化疗起到了重要的作用。然而非小细胞肺癌对化疗并不十分敏感，使得老年晚期非小细胞肺癌患者从目前的化学治疗中获益率较低，甚至是靶向治疗药物，也不能改变现状。华蟾素是一种毒副反应轻微的抗肿瘤中药，能够有效的抑制肿瘤细胞的生长，已被广泛的应用于临床。本文以老年Ⅲ、Ⅳ期非小细胞肺癌作为研究对象，通过化疗与华蟾素治疗的对比，观察中位生存期，生存质量，化疗毒副反应等指标，为中晚期老年非小细胞肺癌提供有效的治疗方案。方法：前瞻性分析2006年8月-2008年3月间大连医科大学附属第一医院肿瘤科Ⅲ、Ⅳ期老年非小细胞肺癌患者60例，进行随机分组，华蟾素组30例，化疗组30例。华蟾素组，华蟾素注射液20ml加入5%GS/NS500ml静脉滴注，每日1次，连续4周为1疗程，用药期间停用其它中药及免疫制剂。化疗组，可按患者情况选用第三代化疗药物加含铂方案(NVB\TXL\GEM+DDP\CBP方案)。观察指标是中位生存期，生存质量，肿瘤缓解和稳定率，治疗的毒副反应及经济因素。在2个周期后评价治疗后实体肿瘤的变化。随访时间一年。结果：1.中位生存期：华蟾素组335天，化疗组280天，显示华蟾素组中位生存期比化疗组长；半年生存率分别为75.65%，56.83%，一年生存率分别为34.73%，28.24%，统计学无显著差异（P0.05）。2.二组肿瘤缓解率比较，华蟾素组总缓解率(CR+PR)为10%，化疗组23.3%，统计学无显著性差异（P0.05）；两组肿瘤稳定率(CR+PR+NC)分别为63.3%，73.3%，差异无统计学意义（P0.05）。3.在生存质量改善方面，华蟾素组生活质量改善率是63.3%，化疗组是30%，二组治疗后生存质量改善率比较，华蟾素组优于化疗组(P0.01)。4.比较两组治疗不良反应，包括血液学毒性、肝肾功能损伤，和普通毒性反应如恶心呕吐等。白细胞减少发生率在华蟾素组是3.3%，化疗组是73.3%；中性粒细胞减少发生率在华蟾素组是3.3%，化疗组是60%；在化疗组ALT、AST、BUN、Cr水平治疗后都有明显升高，而华蟾素组各指标无明显变化。恶性，呕吐及腹泻的发生率化疗组明显高于华蟾素组。华蟾素组的不良反应发生率显著低于化疗组（P0.01)。结论：在生存时间和肿瘤缓解方面华蟾素和化疗的疗效相当，但是在生活质量和不良反应方面华蟾素表现出明显的优势。因此，在Ⅲ、IV期老年NSCLC的治疗中，华蟾素是一种提高患者生活质量，延长生存期，毒副作用小且经济安全的治疗手段，达到了“带瘤生存”的目的。关键词：非小细胞肺癌老年肺癌化疗华蟾素ComparisonofchemotherapyandcinobufotalinforelderlyadvancedNon-Sma11Ce11LungCancerMasterdegreecandidate:ZhuLinSupervisor:ProfessorCuiXiaonanMajor:OncologyAbstractObjective:Lungcancer,included80percentofnon-smallcelllungcancer(NSCLC),isoneofthemajorcausesofmalignanttumors-associateddeath,themorbidityandmortalityoflungcancertrendtoascendstraightlyinchina.InNSCLCpatients,mostpatientsatthetimeofdiagnosiswereatadvancedstageandlosttheopportunityofsurgicaltherapy.ChemotherapyplaysanimportantpartinthewholetherapyofadvancedNSCLC.HoweverNSCLCisnotinsensitivetochemotherapy,theadvancedstageelderlyNSCLCreceivedlittlebenefitfromthepresentchemotherapy.eventhetargetdrugsuchasIressa,ectcouldn’tchangethepuzzlingtherapyofadvancedNSCLC.Cinobufotalinisapopularanti-tumordrugwithlittleadversereactioninTraditionalChineseMedicine,whicheffectiveandmarkedlyinhibitedtumorcellgrowth,andwidelyusedinclinic.ThisstudywasdesignedtoevaluatemediansurvivaltimeandqualityoflifeforthepatientswithstageIII/IVelderlyNSCLCbychemotherapyandcino-bufotalin.SoastosearchtheoptimaltreatmentstrategyforelderlypatientswithadvancedNSCLC.Methods:Theprospectivetrialwasperformedintheoncologydepartmentofthe1staffiliatedhospitalofDaLianMedicalUniversity.DuringAugust2006andMarch2008.60patientswithahistologicallyconfirmeddiagnosisofstageIII/IVNSCLCwereenrolled.Theywererandomlydividedintotwogroups.Therein,30patientsreceivetreatmentofcinobufotalin,30patientsreceivechemotherapy.Projectforthecino-bufotalingroup:withcinobufaciniinjection20mlinto5%GS/NS500mlintravenousdrip,oncedaily,continuedfor4weekspercourse,stopingothertherapyintheperiodoftreatmentsuchasotherTraditionalChineseMedicineandimmunomodulator.Projectforchemotherapygroup:Platinum-basedchemotherapywereadoptedeitherNVB/TXL/GEM/TXT+DDP/CBPregimenwasadopted.Theendpointsweremediansurvivaltime,qualityoflife,tumorresponserate,tumorcontrolrate,theadversereactionofthetherapyandeconomicfactor.Toevaluatetheefficacyofthetherapytosolidtumorafter2cycles.Thefollow-uptimewas1years.Results:1.Themediansurvivaltime:thecinobufotalingroupwas335days,thechemotherapygroupwas280days,thecinobufotalingroupshowedlongermediansurvivaltimethanthatofthechemotherapygroup.Half-yearsurvivalratewas75.65%，56.83%respectively，one-yearsurvivalratewas34.73%，28.24%respectively，therewerenostatisticalsignificancebetweenthetwogroups(P0.05).2.Tumorresponserate(CR+PR)ofthecinobufotalingroupwas10%,and23.3%ofthechemotherapygroup,nostatisticalsignificancewasshowedbetweenthetwogroups(P0.05).Thetumorcontrolrate(CR+PR+NC)ofthecinobufotalingroupwas63.3%，and73.3%ofthechemotherapygroup，therewerenostatisticalsignificancebetweenthem.3.Asforqualityoflife,theimprovementrateofwhichinthecinobufotalingroupwas63.3%,wasmuchhigherthanthatofthechemotherapygroupwith30%improvementrateofqualityoflife(P0.01).4.Comparedwiththeadversereactionofthetwogroups,includinghematologictoxicities，Liverandrenaltoxicities,andcommontoxicreactionsuchasnausea,vomitingandsoon.Theincidencerateofhypoleucocytosisinthecinobufotalingroupwas3.3%,andthechemo-therapygroupwas73.3%.incidencerateofNeutrophilicgranulocytopeniainthecinobufotalingroupwas3.3%,andthechemotherapygroupwas60%.ThelevelofALT、AST、BUN、Crinthechemotherapygroupwassignificantlyincreased,thecinobufotalingrouphadnoobviouslychange.Theincidenceofnausea,vomitinganddiarrheawassignificantlyhigherthanthatincinobufotalingroup.Theincidencerateofadversereaction,thecinobufotalingroupwassign