肺癌的内科治疗课件.ppt

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1、肺癌的内科治疗,1,呼吸病区：王 洁,肺癌内科治疗进展,肺癌的内科治疗,2,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,肺癌的内科治疗,3,肺癌的内科治疗,4,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,肺癌的内科治疗,5,2005 Est

2、imated US Cancer Deaths*,ONS=Other nervous system. Source: American Cancer Society, 2005.,Men295,280,Women275,000,27%Lung and bronchus 15%Breast 10%Colon and rectum 6%Ovary 6%Pancreas 4%Leukemia 3%Non-Hodgkin lymphoma 3%Uterine corpus 2%Multiple myeloma 2%Brain/ONS 22% All other sites,Lung and bronc

3、hus31% Prostate10% Colon and rectum10% Pancreas5% Leukemia4% Esophagus4% Liver and intrahepatic3%bile duct Non-Hodgkin 3% Lymphoma Urinary bladder3% Kidney3% All other sites 24%,肺癌的内科治疗,6,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,肺癌的内

4、科治疗,7,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,肺癌的内科治疗,8,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,肺癌的内科治疗,9,NSCLC: 分期及生存,Mountain. Chest. 1997;1710-1717.,Stage at Diagnosis,

5、St I,St II,St IIIA,St IIIB,St IV,肺癌的内科治疗,10,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,肺癌的内科治疗,11,肺癌的内科治疗,12,NSCLC：复发形式,肺癌的内科治疗,13,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

6、铂类联用，但样本量太小，不足以检测疗效。,肺癌的内科治疗,14,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,肺癌的内科治疗,15,化疗方案,顺铂 80 mg/m 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/

7、m x 3 days per cycle or NVB 30 mg/m weekly or 长春新碱 4 mg/m weekly or 长春地辛 3 mg/m weekly,肺癌的内科治疗,16,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 %,肺癌的内科治疗,17,总生存期,Control,Chemotherapy,Years,肺癌的内科治疗,18,无病生存,Control,Chemotherapy,Years,

8、肺癌的内科治疗,19,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%,肺癌的内科治疗,20,Correlation between stage and activity of Chemotherapy,- positive,- negative,- not tested,肺癌的内科治疗,21,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 h

9、avalier) ASCO 2003JLCRG (Kato) ASCO 2004JBR 10 (Winton) ASCO 2004CALGB (Strauss),肺癌的内科治疗,22,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？,肺癌的内科治疗,23,选择哪些患者？,适应症： 1.IB,II,IIIA期患者 2.PS评分0-1 3. 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,肺癌的内

10、科治疗,24,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,肺癌的内科治疗,25,新辅助治疗,增加肿瘤的手术控制率 减少肿瘤的微转移,肺癌的内科治疗,26,新辅助化疗,肺癌的内科治疗,27,新辅助治疗：SWOG 9900,泰素 225 mg/m2 卡铂 AUC = 6 X 3 cycles,手术,R A N D O M I Z E,手术,Stage IB, II and IIIA (T3N1) N= 374/600,Primary Endpoint: 33% improvement in the expected 2.7 medians survival for su

11、rgery alone,Pisters K, et al,ASCO Abstract # 7012:,肺癌的内科治疗,28,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,肺癌的内科治疗,29,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,肺癌的内科治疗,30,可切除的 N2 NSCLC: INT 0139 Trial,Cispl

12、atin, 50 mg/m2 IVPB d1, 8, 29, 36 Etoposide, 50 mg/m2 IVPB d1-5, 29-33 Thoracic 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 etoposide X 2 cycles,诱导治疗,Albain KS et al,ASCO Abstract #7014,肺癌的内科治疗,31,INT 0139 Update,Overall Survival,Median FU 81 months,肺癌的内科治疗,32,Overall Su

13、rvival 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 0139 Update,肺癌的内科治疗,33,肺叶切除的总生存 Subset VS Matched CT/RT Subset,% Alive,0,25,50,75,100,Months from Randomization

14、,0,12,24,36,48,60,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,/,MS,34 mos. 22 mos.,5 yr OS 36% 18%,CT/RT/S,CT/RT,INT 0139,肺癌的内科治疗,34,Months from Randomization,全肺切除的总生存 Subset VS Matched CT/RT Subset,MS 3 yr OS 5 yr OS,19 mos. 36% 22%,CT/RT/S,CT/RT,% Alive,0,25,50,75,100,0,12,24,36,48,60,/,/,/,/,/,/,

15、/,/,/,/,29 mos. 45% 24%,INT 0139 Update,肺癌的内科治疗,35,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? Restaging mediastinoscopy/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,肺癌的内科治疗,36,Message: Surgical resection does not offer a survival advantage over radiothe

16、rapy 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,肺癌的内科治疗,37,2005 NCCN临床肿瘤指南多学科治疗：辅助化疗,基于IALT研究，对术后辅助化疗进行修订 IA期: T1N0 不进行辅助治疗 I

17、B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,肺癌的内科治疗,38,2005 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,肺癌的内科治疗,39,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 高危者

18、：化疗(2B) 化疗方案 含铂二药联合方案,肺癌的内科治疗,40,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,肺癌的内科治疗,41,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,肺癌的内科治疗,42,LAMP: Randomized Phase II Study of 3 Chemor

19、adiation Schedules for Stage III NSCLC,Arm 1: Sequential Chemo/XRT: Carbo AUC 6 + Pac 200 mg/m2 Q3 wks x 2 XRT 63 Gy/7 wks Arm 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 Ch

20、emo: XRT 63 Gy/7 wks + weekly Carbo AUC 2 + Pac 45 mg/m2 Carbo AUC 6 + Pac 200 mg/m2 Q3 wks x 2,肺癌的内科治疗,43,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%

21、) 30(33%) KPS: 70-80 25(27%) 23(31%) 22(24%) 90-10067(73%) 51(69%) 70(76%) % Weight Loss 5%67(73%) 47(64%) 66(72%) 5-10% 25(27%) 27(36%) 26(28%) Stage:IIIA33(36%)28(38%) 35(38%) IIIB59(64%)46(62%) 57(62%),肺癌的内科治疗,44,T/CRTHistorical 1 yr 59% 58% 2 yr 31% 31% Median 13.0 mo 14.5,T/CT/C/RT Historical 1

22、 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,Arm 3,Arm 2,肺癌的内科治疗,45,SWOG 9504: Treatment,Concurrent Chemoradiation PE:Cisplatin 50 mg/m2 IV d 1, 8, 29, 36Etoposide 50 mg/m2 IV d 1-5, 29-33 RT:45 Gy (1.8 Gy/fractio

23、n)16 Gy boost (2 Gy/fraction),Consolidation Docetaxel 75 mg/m2 IV X 1 cycle Docetaxel 75-100 mg/m2 IV X 2 cycles (every 3 weeks),Gaspar LE, et al. Proc Am Soc Clin Oncol 2001;20:315a. (abstr 20:315a. (abstr 311:899-909 Current ASCO Guidelines: Platinum doublets or non-platinum doublets are standard

24、for advanced NSCLC pts with good PSPfister et al. J Clin Oncol. 2004;22:330-353,肺癌的内科治疗,56,Advanced NSCLCUS FDA Approved Therapies,1994 vinorelbine/cisplatin and vinorelbine 1998 gemcitabine/cisplatin 1998 paclitaxel/cisplatin 1999 docetaxel (after platinum) 2003 docetaxel/cisplatin 2003 gefitnib (a

25、fter platinum and docetaxel) 2004 pemetrexed (after platinum) 2004 erlotinib (after 1 prior chemotherapy),肺癌的内科治疗,57,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,肺癌的内科治疗,58,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

26、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,肺癌的内科治疗,59,月,概率,Log-rank p = 0.03,肺癌的内科治疗,60,肺癌的内科治疗,61,肺癌的内科治疗,62,吉西他滨,最佳支持治疗,月,概率,Log-rank p = 0.84,肺癌的内科治疗,63,ECOG 1594: Study Design,Stratification: Stage: IIIB vs IV PS: 01 vs 2 Wt Loss: 5% vs 5% CNS Mets: no vs yes,Arm A: Cisplatin + P

27、aclitaxel Paclitaxel: 135 mg/m2/24 h Day 1 Cisplatin: 75 mg/m2 day 2,q3wk,Arm D: Carboplatin + Paclitaxel Paclitaxel: 225 mg/m2/3 h Day 1 Carboplatin: AUC 6 Day 1,Arm C: Cisplatin + Docetaxel Docetaxel: 75 mg/m2 Day 1 Cisplatin: 75 mg/m2 Day 1,Arm B: Cisplatin + Gemcitabine Gemcitabine: 1000 mg/m2 D

28、ays 1, 8, 15 Cisplatin: 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.,R A N D O M I Z E,肺癌的内科治疗,64,E1594,肺癌的内科治疗,65,ECOG 1594:Analysis of Toxicity,22,66,7,62,11,56,27,28,0,10,20,30,40,50,60,70,3 级,

29、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,肺癌的内科治疗,66,TAX326 Study Design （泰素蒂铂类Vs NVB+铂类）,RANDOMIZE,Stratifiication Factors: Stage of Disease IIIB vs. IV and Region US/Canada South America Europe/Lebanon Israel SouthAfrica/AustraliaNew Zealand,Response assessment every 2 cycles,泰素蒂 75mg/

30、m2 IV 卡铂 AUC 6 IV Q 3 wks (TCb),诺维苯 25mg/m2 IV D 1, 8, 15 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,100,80,60,40,20,0,Survival (%),0,P = .657, adjustedlog-rank test,TCb,VC,1-y survival 46% vs 41% with VC 2-y survival 21% vs 14% with VC Median su

31、rvival: 11.3 vs 10.1 mo,P = .044, adjusted log-rank test,1-y survival 38% vs 40% with VC 2-y survival 18% vs 14% with VC,肺癌的内科治疗,68,R A N D O M I Z E,Protocol Schema,Stratification Weight loss in previous 6 months: 5% vs 5% Disease stage: IIIB with effusion, IV Brain metastases: Presence or absence,

32、含铂方案Vs非铂方案,ASCO Abstract #7025,肺癌的内科治疗,69,Coalition Trial,Survival by Treatment Arm,肺癌的内科治疗,70,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.,肺癌的内科治疗,71,卡铂Vs顺铂,Does it matter for advanced disease?,肺癌的内科治疗,72,NSCLC: 90年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla,

33、 2004,肺癌的内科治疗,73,NSCLC: 90年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla, 2004,M O N T H S,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.,肺癌的内科治疗,74,Carbo vs. Cis Meta-analysis Overall survival with cisplatin-based compared w

34、ith carboplatin-based chemotherapy Hotta, K. et al. J Clin Oncol; 22:3852-3859 2004,肺癌的内科治疗,75,Carbo vs. Cis Meta-analysis Overall survival with cisplatin plus new agents compared with carboplatin plus new agents Hotta, K. et al. J Clin Oncol; 22:3852-3859 2004,肺癌的内科治疗,76,一线化疗: 怎样选择最好的联合方案?,疗效与生存? 生

35、活质量? 毒性? 病人的基础状态? 费用?,肺癌的内科治疗,77,Weekly Paclitaxel with Carboplatin 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 of

36、f )*,Paclitaxel 100 mg/m2 + Carboplatin AUC=2 (weekly for 3 wks, 4th wk 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,肺癌的内科治疗,78,Weekly Pac

37、litaxel with Carboplatin Followed by Maintenance Paclitaxel vs.Observation for Advanced NSCLC,Efficacy/Toxicity Arm 1 Arm 2 Arm 3 Median 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) (

38、p0.20 vs 1) Neutropenia grade 4 22% 8% 19% Thrombocytopenia grade 4 5% 2% 1% Neuropathy grade 3 5% 3% 13% Belani et al, JCO 21:2933-39, 2003,肺癌的内科治疗,79,S T R A T I F Y,ECOG PS 0 2. C.Camps, et al. Proc Am Soc Clin Oncol 2003;625. (abstr 2514),肺癌的内科治疗,87,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

39、 一线化疗 二线/三线化疗 分子靶向治疗 化疗预防,肺癌的内科治疗,88,Targeted Therapy: Validates the “Targeted Therapy” development strategy But, thus far, offer marginal benefit,肺癌的内科治疗,89,抗肿瘤生物靶点治疗(临床),EGFR HER2 TK gefitinib/ erolinib (NSCLC) EGFR 单抗(人) Herceptin(乳癌/Chemo协同), C225(结直肠癌, 乳癌, NSCLC) VEGF单抗 Avastin(结直肠癌, NSCLC),肺癌的

40、内科治疗,90,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,pY,pY,p

41、Y,肺癌的内科治疗,91,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,肺癌的内科治疗,92,IDEAL 1 30(1 Suppl 1):30-8,51,54,疾病控制率(),19,18,有效率（）,500mg/d,250mg/d,IDEAL-1,N210

42、,35,43,症状改善率(),9,12,有效率（）,500mg/d,250mg/d,IDEAL- 2,N216,肺癌的内科治疗,95,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，推荐结论是250mg/d。因为500mg/d的疗效无增加，但毒性更大。,肺癌的内科治疗,96,ISEL:IRE

43、SSA survival evaluation in lung cancer (Trial 709),曾接受1-2种化疗方案的晚期NSCLC患者接受吉非替尼(易瑞沙)与最佳支持治疗并安慰剂随机对照III期临床试验,肺癌的内科治疗,97,ISEL：Bankground,共入组1692 NSCLC 病人(2003.7.15-2004.8.2) 在28个国家的210个中心开展 其中342例病人(22%)为东方人 主要终点指标：总体生存期 次要终点指标（治疗失败时间，客观缓解和生活质量），2005年2月的安全性情况 预先设计对东方人进行亚组分析,肺癌的内科治疗,98,IRESSA(250 mg/day

44、),1 end-point Survival 2 end-points TTF ORR QoL, symptoms Safety Exploratory end-point Tumour biomarker analysis (eg EGFR),1692 patients in 210 centers across 28 countries Randomized (2:1 ratio),Placebo + BSC,CT, chemotherapy; BSC, best supportive care; EGFR, epidermal growth factor receptor; TTF, t

45、ime to treatment failure; ORR, objective response rate; QoL, quality of life,Patients Locally advanced or metastatic NSCLC 1 or 2 prior CT regimens Intolerant to most recent CT regimen or progression 90 days of last CT cycle,ISEL trial design,肺癌的内科治疗,99,0,2,4,6,8,10,12,14,16,Time (months),At risk:,1

46、692,1347,877,485,252,104,31,Median, months 1-year survival, % Logrank HR (95% CI), 0.89 (0.77, 1.02); p=0.087Cox regression analysis, p=0.030,IRESSA 5.6 27,Placebo 5.1 21,0.0,0.2,0.4,0.6,0.8,1.0,Proportionsurviving,IRESSA,Placebo,CI, confidence interval; HR, hazard ratio,Median follow-up: 7 months (range 315); 58% deaths,ISEL: