肺癌的内科治疗.ppt

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1、,呼吸病区：王 洁,肺癌内科治疗进展,非小细胞肺癌内科治疗研究进展,NSCLC:NSCLC的流行病学及诊断分期 早期可手术切除NSCLC的辅助化疗 局部晚期不可手术切除NSCLC同步化放疗 IIIb(胸水)/IV期NSCLC姑息化疗 分子靶向治疗SCLC的全身治疗,肺癌的分子异常,常见的基因改变,烟草,对细胞外信号异常应答细胞周期失控凋亡机制失控接触抑制丧失获得转移能力血管生成永生化自分泌生长,肺泡不典型增生,癌前腺瘤,肺癌,原位癌,异型性变,支气管化生,正常上皮,2005 Estimated US Cancer Deaths*,ONS=Other nervous system.Source:

2、American Cancer Society,2005.,Men295,280,Women275,000,27%Lung and bronchus15%Breast10%Colon and rectum 6%Ovary 6%Pancreas 4%Leukemia 3%Non-Hodgkin lymphoma 3%Uterine corpus 2%Multiple myeloma 2%Brain/ONS22%All other sites,Lung and bronchus31%Prostate10%Colon and rectum10%Pancreas5%Leukemia4%Esophagu

3、s4%Liver and intrahepatic3%bile ductNon-Hodgkin 3%Lymphoma Urinary bladder3%Kidney3%All other sites 24%,高龄肺癌发病概况,肺癌患者年龄70岁占40%加拿大2002年统计 男:75-79岁肺癌发病达高峰 女:70-74岁肺癌发病达高峰意大利：65岁以上肺癌患者大约占60%我国肺癌发病率40岁以后上升，70岁达高峰,鳞癌(30%)男性最常见主要与吸烟相关（剂量相关）局部播散倾向痰中较易检出高表达具有解毒和抗氧化特性的基因编码蛋白,非小细胞肺癌(NSCLC)病理类型,腺癌(30-50%)在女性和不

4、吸烟者中最常见的肺癌类型病变常发于外周全世界发病率上升高表达与小气道与免疫相关的基因编码蛋白K-ras 突变常见支气管肺泡癌是其一个亚型,NSCLC 分期,淋巴结,主支气管,对侧淋巴结,远处器官转移,胸壁侵犯,NSCLC:分期及生存,Mountain.Chest.1997;1710-1717.,Stage at Diagnosis,St I,St II,St IIIA,St IIIB,St IV,肺癌内科治疗研究进展,NSCLC:NSCLC的流行病学及诊断分期早期可手术切除NSCLC的辅助化疗局部晚期不可手术切除NSCLC同步化放疗IIIb(胸水)/IV期NSCLC姑息化疗 分子靶向治疗SCL

5、C的全身治疗,NSCLC：复发形式,背景,过去二十年来，非小细胞肺癌采用辅助化疗，特别是早期的非小细胞肺癌，由于缺乏有力的证据，治疗效果仍然不明确。第一代的临床试验设计得不完善，使用的药物有效率不高。第二代的临床研究以老的化疗药物与铂类联用，但样本量太小，不足以检测疗效。,IALT临床研究设计,R,Chemotherapy,Control,Thoracic Radiotherapy 60 Gy*optional,but predefined by N stage at each center,完全切除 NSCLC,ASCO,Chicago,June 2,2003,化疗方案,顺铂 80 mg/m

6、 q 3 weeks x 4 or 100 mg/m q 4 weeks x 3 or 4 or 120 mg/m q 4 weeks x 3+Vp-16 100 mg/m x 3 days per cycleor NVB 30 mg/m weeklyor 长春新碱 4 mg/m weeklyor 长春地辛 3 mg/m weekly,结 果,化疗对照 N 932935 中位生存期50.8 months44.4 months 中位无病生存期40.2 months30.5 months 5-年生存率44.5%40.4%5-年无病生存率39.4%34.3%,总生存期,Control,Chemoth

7、erapy,Years,无病生存,Control,Chemotherapy,Years,总 结,5年总生存率提高4.1%（40.4%Vs 44.5%）p0.03,5年无病生存提高5.1%(34.3%VS 39.4%，p0.003)致死性毒性 0.8%,Correlation between stage and activity of Chemotherapy,-positive,-negative,-not tested,早期(I-IIIa)完全切除的NSCLC,基于4组随机对照研究结果，对IB-III完全切除的NSCLC,辅助化疗是标准的治疗方法,ASCO 2003 IALT(Le hava

8、lier)ASCO 2003JLCRG(Kato)ASCO 2004JBR 10(Winton)ASCO 2004CALGB(Strauss),有待解决的问题,选择哪些患者？选择何种化疗方案？化疗的时机？化疗周期？分子靶向药物如何与化疗结合？,选择哪些患者？,适应症：1.IB,II,IIIA期患者2.PS评分0-13.高危因素的IA期肿瘤 2cm低分化 分子标记物指标Dr.Strass 的个人观点禁忌症：1.IA期 2.全肺切除术？3.年龄75岁？4.细支气管肺泡癌5.有合并症 6.术后恢复慢,化疗的时机？,一般术后4-6周开始化疗。,化疗周期？,推荐4个化疗周期,新辅助治疗,增加肿瘤的手术控

9、制率减少肿瘤的微转移,新辅助化疗,新辅助治疗：SWOG 9900,泰素 225 mg/m2卡铂 AUC=6X 3 cycles,手术,RANDOMIZE,手术,Stage IB,II and IIIA(T3N1)N=374/600,Primary Endpoint:33%improvement in the expected 2.7 medians survival for surgery alone,Pisters K,et al,ASCO Abstract#7012:,无疾病进展生存期,HR=0.80 0.59-1.07,p=0.14,median F/U 31 mo,SWOG 9900,

10、总生存,HR=0.84 0.60-1.18,p=0.32,SWOG 9900,Median,1 yr,2 yr,Preop,47 mo,82%,69%,Control,40 mo,79%,63%,Median FU 31 months,可切除的 N2 NSCLC:INT 0139 Trial,Cisplatin,50 mg/m2 IVPB d1,8,29,36Etoposide,50 mg/m2 IVPB d1-5,29-33Thoracic RT,45 Gy(1.8 Gy/d),begin d1,疾病无进展者,手术,继续放疗至 61 Gy,巩固化疗cisplatin plus etoposi

11、deX 2 cycles,诱导治疗,Albain KS et al,ASCO Abstract#7014,INT 0139 Update,Overall Survival,Median FU 81 months,Overall Survival by Pathologic Nodal Status,No surgery(n=38),Pathologic N0(n=76),Pathologic N1-3,unknown(n=88),p 0.0001,%Alive,0,25,50,75,100,Months from Randomization,0,20,40,60,80,100,120,INT

12、0139 Update,肺叶切除的总生存Subset VS Matched CT/RT Subset,%Alive,0,25,50,75,100,Months from Randomization,0,12,24,36,48,60,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,MS,34 mos.22 mos.,5 yr OS 36%18%,CT/RT/S,CT/RT,INT 0139,Months from Randomization,全肺切除的总生存Subset VS Matched CT/RT Subset,MS3 yr OS5 yr OS,

13、19 mos.36%22%,CT/RT/S,CT/RT,%Alive,0,25,50,75,100,0,12,24,36,48,60,/,/,/,/,/,/,/,/,/,/,29 mos.45%24%,INT 0139 Update,部分N2病人可能为外科手术受益者：外科因素:能行肺叶切除的N2病人 肿瘤因素：能淋巴结完全清扫者有更长的生存期 Role for post treatment PET?Restagingmediastinoscopy/VATS/EUS?,N2 病人是否外科治疗需肺癌多学科讨论决定,局部晚期（N2）NSCLC,Message:Surgical resection d

14、oes not offer a survival advantageover radiotherapy in patients with clinically operable(INT 0319)or inoperable(EORTC 8941)stage III N2 disease.Concurrent chemoradiotherapy is the standard of care.Pneumonectomies should be avoided.,Locally Advanced N2 Lung Cancer,2005 NCCN临床肿瘤指南多学科治疗：辅助化疗,基于IALT研究，对

15、术后辅助化疗进行修订 IA期:T1N0 不进行辅助治疗 IB期:T2N0 推荐术后进行辅助化疗 II期:T1-2N1 推荐术后辅助化疗或放疗(2B)+化疗 期 术后可选择单用化疗或放疗(2B)+化疗,2005 NCCN临床肿瘤指南多学科治疗：辅助化疗,对于临床分期N2阴性而术后病理分期N2阳性者,术后可以选择化疗或观察(2B)或联合放化疗(2B)T4N0-1同叶内卫星结节者,术后需辅助化疗 辅助化疗应选择含铂的二药联合方案,术后辅助化疗,基于CALGB9633和BR10研究对于术后辅助化疗的推荐级别：2004 2A 2005 1级 对IA(T1N0)者完全切除术后：2004 观察 2005 高

16、危者：化疗(2B)化疗方案 含铂二药联合方案,肺癌内科治疗研究进展,NSCLC:NSCLC的流行病学及诊断分期早期可手术切除NSCLC的辅助化疗局部晚期不可手术切除NSCLC同步化放疗IIIb(胸水)/IV期NSCLC姑息化疗 分子靶向治疗SCLC的全身治疗,不能手术局部晚期NSCLC化放疗结合的方式,Sequential:CT RT Concurrent:CT/RT Combinations:CT CT/RT CT/RT CT,LAMP:Randomized Phase II Study of 3 Chemoradiation Schedules for Stage III NSCLC,Ar

17、m 1:Sequential Chemo/XRT:Carbo AUC 6+Pac 200 mg/m2 Q3 wks x 2 XRT 63 Gy/7 wksArm 2:Induction Chemo Concurrent ChemoXRT:Carbo AUC 6+Pac 200 mg/m2 Q3 wks x 2 XRT 63 Gy/7 wks+weekly Carbo AUC 2+Pac 45 mg/m2 Arm 3:Concurrent ChemoXRT Consolidation Chemo:XRT 63 Gy/7 wks+weekly Carbo AUC 2+Pac 45 mg/m2 Ca

18、rbo AUC 6+Pac 200 mg/m2 Q3 wks x 2,LAMP:Pre-Treatment Characteristics,CT RTCT CT+RTCT+RT CT(N=92)(N=74)(N=92)Age:7074(80%)53(72%)69(75%)70+18(20%)21(28%)23(25%)Gender:Male63(68%)54(73%)62(67%)Female29(32%)20(27%)30(33%)KPS:70-80 25(27%)23(31%)22(24%)90-10067(73%)51(69%)70(76%)%Weight Loss 5%67(73%)4

19、7(64%)66(72%)5-10%25(27%)27(36%)26(28%)Stage:IIIA33(36%)28(38%)35(38%)IIIB59(64%)46(62%)57(62%),T/CRTHistorical 1 yr 59%58%2 yr 31%31%Median 13.0 mo 14.5,T/CT/C/RT Historical 1 yr 53%58%2 yr 22%31%Median 12.8mo 14.5mo,_,_,-,-,T/C/RTT/C Historical 1 yr 64%58%2 yr 33%31%Median 16.1mo 14.5mo,_,-,Arm 1,

20、Arm 3,Arm 2,SWOG 9504:Treatment,Concurrent ChemoradiationPE:Cisplatin 50 mg/m2 IV d 1,8,29,36Etoposide 50 mg/m2 IV d 1-5,29-33RT:45 Gy(1.8 Gy/fraction)16 Gy boost(2 Gy/fraction),ConsolidationDocetaxel 75 mg/m2 IV X 1 cycleDocetaxel 75-100 mg/m2 IV X 2 cycles(every 3 weeks),Gaspar LE,et al.Proc Am So

21、c Clin Oncol 2001;20:315a.(abstr&poster 1255),Phase II SWOG Trial(S9504):Results,Survival Median27 mos 18-43 mos 1-year survival76%67%-85%2-year survival54%43%-64%3-year survival40%24%-55%,0%,20%,40%,60%,80%,100%,0,12,24,36,48,Months After Registration,SWOG 9504Progression-Free Survival,MedianN Even

22、ts in Months83 56 16,100%,SWOG 9504Overall Survival,Gaspar:ASCO 2001,SWOG 9504(PE/RT TXT)vs SWOG 9019(PE/RT PE):Patient Characteristics,SWOG 9504 SWOG 9019No.Patients8350Median age6058Male/Female61/2241/9PS:0-17850 2 5 0Stage:n(%)T4 N0-131(37)18(36)T4 N222(27)12(24)N330(36)20(40),SWOG 9504(PE/RT TXT

23、)vs SWOG 9019(PE/RT PE):Survival(median f/u 28 mos),SWOG 9504SWOG 9019Med Surv 27 mos 15 mos 95%CI 18 43 mos 10 22 mosSurvival rates 1 year 76%67-85 58%44-72 2 year 54%43-64 34%21-47 3 year 40%24-55 17%7-27 4 year 39%17%,Gaspar LE,et al.Proc Am Soc Clin Oncol 2001;20:315a.(abstr&poster 1255),Current

24、 Status of Chemoradiotherapy in Stage III NSCLC,Adapted from Pisters:ASCO,2000*S9504,2005 NCCN临床肿瘤指南多学科治疗：辅助化疗,对于临床分期N2阴性而术后病理分期N2阳性者,术后可以选择化疗或观察(2B)或联合放化疗(2B)T4N0-1同叶内卫星结节者,术后需辅助化疗 辅助化疗应选择含铂的二药联合方案,肺癌内科治疗研究进展,NSCLC:NSCLC的流行病学及诊断分期早期可手术切除NSCLC的辅助化疗局部晚期不可手术切除NSCLC同步化放疗IIIb(胸水)/IV期NSCLC姑息化疗 分子靶向治疗SCLC

25、的全身治疗,治疗原则,控制症状提高生活质量延长生存期,联合化疗作为NSCLC的一线治疗,Good PS Patients1990s:Platinum-based CT standardNSCLC Collaborative Group BMJ.1995;311:899-909Current ASCO Guidelines:Platinum doublets or non-platinum doublets are standard for advanced NSCLC pts with good PSPfister et al.J Clin Oncol.2004;22:330-353,Adva

26、nced NSCLCUS FDA Approved Therapies,1994 vinorelbine/cisplatin and vinorelbine1998 gemcitabine/cisplatin1998 paclitaxel/cisplatin1999 docetaxel(after platinum)2003 docetaxel/cisplatin2003 gefitnib(after platinum and docetaxel)2004 pemetrexed(after platinum)2004 erlotinib(after 1 prior chemotherapy),

27、NSCLC:一线化疗,化疗 Vs BSC？有无最好的铂类联合方案？含铂方案Vs非铂方案？卡铂 Vs 顺铂？化疗靶向治疗Vs化疗,治 疗,长春瑞滨 30 mg/m2，第1、8天 每3周+最佳支持治疗最佳支持治疗(BSC),紫杉醇 200 mg/m2 第1天 每3周+BSC最佳支持治疗,泰索帝 100 mg/m2 第1天 每3周+BSC最佳支持治疗,吉西他滨 1000 mg/m2 第1、8和15天 每4周+BSC最佳支持治疗,月,概率,Log-rank p=0.03,吉西他滨,最佳支持治疗,月,概率,Log-rank p=0.84,ECOG 1594:Study Design,Stratifica

28、tion:Stage:IIIB vs IVPS:01 vs 2Wt Loss:5%vs 5%CNS Mets:no vs yes,Arm A:Cisplatin+PaclitaxelPaclitaxel:135 mg/m2/24 h Day 1 Cisplatin:75 mg/m2 day 2,q3wk,Arm D:Carboplatin+PaclitaxelPaclitaxel:225 mg/m2/3 h Day 1Carboplatin:AUC 6 Day 1,Arm C:Cisplatin+DocetaxelDocetaxel:75 mg/m2 Day 1Cisplatin:75 mg/

29、m2 Day 1,Arm B:Cisplatin+GemcitabineGemcitabine:1000 mg/m2 Days 1,8,15Cisplatin:100 mg/m2 Day 1,q4wk,q3wk,q3wk,Schiller JH,et al.Proc ASCO 36th Annual Meeting.2000;19:abstr 2.Schiller JH,et al.N Engl J Med.2002;346:92-98.,RANDOMIZE,E1594,ECOG 1594:Analysis of Toxicity,22,66,7,62,11,56,27,28,0,10,20,

30、30,40,50,60,70,3 级,4 级,%,泰素/顺铂,吉西他滨/顺铂,多西紫杉醇/顺铂,泰素/卡铂,PS2的病人的3-4级毒性发生百分比,TAX326 Study Design（泰素蒂铂类Vs NVB+铂类）,RANDOMIZE,Stratifiication Factors:Stage of DiseaseIIIB vs.IVand RegionUS/Canada South AmericaEurope/LebanonIsraelSouthAfrica/AustraliaNew Zealand,Response assessment every 2 cycles,泰素蒂 75mg/m

31、2 IV 卡铂 AUC 6 IV Q 3 wks(TCb),诺维苯 25mg/m2 IV D 1,8,15&22顺铂 100mg/m2 IV D 1Q 4 wks(VC),泰素蒂 75mg/m2 IV顺铂 75mg/m2 IV Q 3 wks（TC）,vs.,or,TAX 326 Overall Survival,Fossella et al.J Clin.Oncol.2003;21:3016-3024.,100,80,60,40,20,0,Survival(%),0,3,6,9,12,15,18,21,24,27,30,33,Time(months),TC,VC,100,80,60,40,2

32、0,0,Survival(%),0,P=.657,adjustedlog-rank test,TCb,VC,1-y survival 46%vs 41%with VC2-y survival 21%vs 14%with VCMedian survival:11.3 vs 10.1 mo,P=.044,adjusted log-rank test,1-y survival 38%vs 40%with VC2-y survival 18%vs 14%with VC,RANDOMIZE,Protocol Schema,Stratification Weight loss in previous 6

33、months:5%vs 5%Disease stage:IIIB with effusion,IV Brain metastases:Presence or absence,含铂方案Vs非铂方案,ASCO Abstract#7025,Coalition Trial,Survival by Treatment Arm,Meta-Analysis:1-Y 生存90年代新化疗药物联合作为非铂方案(N=3,307),dAddario et al.J Clin Oncol.2005;23:2926-2936.,卡铂Vs顺铂,Does it matter for advanced disease?,NSC

34、LC:90年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla,2004,NSCLC:90年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla,2004,MONTHS,Carboplatin Cisplatin N=1152 N=1154,8.7,9.8,*No other such trials 1992 2003;*2 trials with paclitaxel,1 with docetaxel,2 with gem.,Carbo vs.Cis Meta-analysisOverall survival with cisplatin-based compared with car

35、boplatin-based chemotherapyHotta,K.et al.J Clin Oncol;22:3852-3859 2004,Carbo vs.Cis Meta-analysisOverall survival with cisplatin plus new agents compared with carboplatin plus new agentsHotta,K.et al.J Clin Oncol;22:3852-3859 2004,一线化疗:怎样选择最好的联合方案?,疗效与生存?生活质量?毒性?病人的基础状态?费用?,Weekly Paclitaxel with C

36、arboplatin Followed by Maintenance Paclitaxel vs.Observation for Advanced NSCLC,Arm 3,Arm 2,Arm 1,Paclitaxel 150 mg/m2+Carboplatin AUC=2(weekly for 6 wks,2 wks off),then Paclitaxel 100 mg/m2+Carboplatin AUC=2(weekly for 6 wks,2 wks off)*,Paclitaxel 100 mg/m2+Carboplatin AUC=2(weekly for 3 wks,4th wk

37、 off)*,Paclitaxel 100 mg/m2(weekly for 3 wks,4th wk off)+Carboplatin AUC=6(d1)*,SCHEMA,Belani et al,JCO 21:2933-39,2003,*Patients with CR,PR or SD randomized to paclitaxel 70 mg/m2/wk or observation,Weekly Paclitaxel with Carboplatin Followed by Maintenance Paclitaxel vs.Observation for Advanced NSC

38、LC,Efficacy/Toxicity Arm 1 Arm 2 Arm 3Median Survival Time 49 wks 31 wks 40 wks(p=0.077 vs 1)(p0.45 vs 1)Median TTP 30 wks 21 wks 27 wks(p=0.01 vs 1)(p0.73 vs 1)1-yr.Survival 47%31%41%(p0.01 vs 1)(p0.20 vs 1)Neutropenia grade 4 22%8%19%Thrombocytopenia grade 4 5%2%1%Neuropathy grade 3 5%3%13%Belani

39、et al,JCO 21:2933-39,2003,STRATIFY,ECOG PS0&1 vs 2StageIIIB vs IV,RANDOMIZE,WeeklyPaclitaxel 100 mg/m2/week x 3Carboplatin AUC=6(Cycle duration 4 weeks,Total 4 cycles)StandardPaclitaxel 225 mg/m2 3Carboplatin AUC=6 day 1(Cycle duration 3 weeks,Total 4 cycles),TAXMEN 12:Phase III Study Schema,*Mainte

40、nance Therapy Paclitaxel 70 mg/m2/week 3 weeks on,1 week off Until Disease Progression,*For patients with CR/PR or SD on both arms,Taxmen 12:Kaplan-Meier Estimates Patient Survival,1.0,0.9,0.8,0.7,0.6,0.5,0.4,0.3,0.2,0.1,0.0,0,8,16,24,32,40,48,56,64,72,80,88,96,104,112,120,128,136,144,152,160,Weekly

41、,Standard,Proportion of Patients Who Survived,Time(Weeks),Message:First set of evidence suggesting we are moving toward customized chemotherapy in lung cancer.Dilemma:Will predictive markers of response to the original treatment translate into a survival benefit in the era of second and third line t

42、herapies?Finally MT with wkly paclitaxel demonstrates significant improvement in survival(76.6 wks with MT vs.49.6 wks without MT,P=0.016)-Role?Can this concept be validated with other agents?,Metastatic Lung Cancer,Message:A platinum or a non-platinum doublet is the standard of care for the first l

43、ine treatment of good performance status patients.Dilemma:Who will switch to a nonplatinum regimen in good PS patients!Overshadowed by efficacy of Chemotherapy/Bevacizumab combination in select patients with non-squamous carcinoma,Metastatic Lung Cancer,FDA 批准的NSCLC二线治疗药物,Docetaxel,Pemetrexed,Erloti

44、nib,NSCLC 二线治疗：泰素蒂 Vs BSC,Shepherd et al 2000,中位生存期(月)1年 生存率(%),Log rank:p=0.01,泰素蒂 75 mg/m2(n=55)最好的支持治疗(n=49),0,3,6,9,12,15,18,21,累计的概率,0.0,0.2,0.4,0.6,0.8,1.0,泰素蒂75 mg/m27.537,最好的支持治疗4.612,月,Hanna1 Camps2,Alimta 和泰索帝及泰索帝单药3周和每周方案的肺癌2线随机III期临床试验,1.JCO 2004;2.C.Camps,et al.Proc Am Soc Clin Oncol 20

45、03;625.(abstr 2514),非小细胞肺癌内科治疗研究进展,NSCLC的流行病学及诊断分期辅助化疗 同步化放疗 姑息化疗 一线化疗 二线/三线化疗分子靶向治疗 化疗预防,Targeted Therapy:Validates the“Targeted Therapy”development strategyBut,thus far,offer marginal benefit,抗肿瘤生物靶点治疗(临床),EGFR HER2 TKgefitinib/erolinib(NSCLC)EGFR 单抗(人)Herceptin(乳癌/Chemo协同),C225(结直肠癌,乳癌,NSCLC)VEGF

46、单抗Avastin(结直肠癌,NSCLC),存活(抗细胞凋亡),PI3-K,表皮生长因子受体酪氨酸激酶(EGFR-TK)激活:癌变的关键驱动因素,EGFR-TK,EGFR,配体,RAS,RAF,SOS,GRB2,PTEN,AKT,STAT3,MEK,基因转录细胞周期进展,DNA,Myc,Myc,Cyclin D1,JunFos,P P,MAPK,增生/成熟,放化疗耐药性,血管形成,转移,Balaban et al 1996;Akimoto et al 1999;Wells 1999;Woodburn 1999;Hanahan 2000;Raymond et al 2000,Cyclin D1,

47、pY,pY,pY,Gefitinib(IRESSATM,ZD1839)Phase II monotherapy trialsin advanced non-small-cell lung cancer(NSCLC),IDEAL 1(Trial 16)IDEAL 2(Trial 39),IDEAL=IRESSA Dose Evaluation in Advanced Lung Cancer,IDEAL 1&2:design schema,Gefitinib 250 mgonce daily,Gefitinib 500 mgonce daily,Received 1 or 2(IDEAL 1)or

48、 2(IDEAL 2)previouschemotherapyregimens,Continue gefitinib until diseaseprogression or unacceptable toxicity,Primary endpoints,Patients,Response rate(both trials)Safety profile(IDEAL 1)Symptom relief(IDEAL 2),IDEAL 1 global trial including Japan,Europe,Australia,and South Africa(JPN=209)IDEAL 2 USA

49、trial,Natale&Zaretsky 2002,RANDOMIZEDD,Gefitinib(Iressa)治疗晚期NSCLC的研究(IDEAL-1,2),IDEAL：Iressa Dose Evaluation in Advanced Lung Cancer IDEAL-1：该研究是一随机、双盲、全球性研究。在欧洲、日本、南美洲等地进行，比较不同剂量的Irassa治疗晚期NSCLC。IDEAL-2：Iressa作为三线药物单药治疗晚期NSCLC的研究。该研究在美国的30个试验中心下进行。,Gefitinib作为三线药物治疗晚期NSCLC的研究,Semin Oncol.2003;30(1

50、Suppl 1):30-8,51,54,疾病控制率(),19,18,有效率（）,500mg/d,250mg/d,IDEAL-1,N210,35,43,症状改善率(),9,12,有效率（）,500mg/d,250mg/d,IDEAL-2,N216,Gefitinib作为三线药物治疗晚期NSCLC的期研究,Oncologist.2003;8(4):303-6.,7.0,4.5,8.9,中位有效期(月),10.6,7.9,13.6,有效率（）,两组合并(n=142),500mg/d(n=76),250mg/d(n=66),结论：Gefitinib用于铂类和多西紫杉醇治疗失败的晚期NSCLC病人，推荐