肺癌的内科治疗课件

1、肺癌的内科治疗1 呼吸病区：王呼吸病区：王 洁洁 肺癌内科治疗进展肺癌内科治疗进展肺癌的内科治疗2非小细胞肺癌非小细胞肺癌内科治疗研究进展内科治疗研究进展肺癌的内科治疗3肺癌的内科治疗4肺癌的分子异常肺癌的分子异常常见的基因改变常见的基因改变烟草烟草对细胞外信号异常应答对细胞外信号异常应答细胞周期失控细胞周期失控凋亡机制失控凋亡机制失控接触抑制丧失接触抑制丧失获得转移能力获得转移能力血管生成血管生成永生化永生化自分泌生长自分泌生长肺泡不典型增生肺泡不典型增生癌前腺瘤癌前腺瘤肺癌肺癌原位癌原位癌异型性变异型性变支气管化生支气管化生正常上皮正常上皮肺癌的内科治疗52005 estimated us

2、 cancer deaths2005 estimated us cancer deaths* *ons=other nervous system.source: american cancer society, 2005.men295,280women275,000lung and bronchus 31%prostate10%colon and rectum10%pancreas5%leukemia4%esophagus4%liver and intrahepatic 3%bile ductnon-hodgkin 3% lymphoma urinary bladder3%kidney3%al

3、l other sites 24%肺癌的内科治疗6高龄肺癌发病概况高龄肺癌发病概况肺癌的内科治疗7鳞癌鳞癌 (30%)(30%)男性最常见男性最常见主要与吸烟相关（剂量相关）主要与吸烟相关（剂量相关）局部播散倾向局部播散倾向痰中较易检出痰中较易检出高表达具有解毒和抗氧化特性的高表达具有解毒和抗氧化特性的基因编码蛋白基因编码蛋白非小细胞肺癌非小细胞肺癌(nsclc)病理类型病理类型腺癌腺癌 (30-50%)在女性和不吸烟者中最常见的在女性和不吸烟者中最常见的肺癌类型肺癌类型病变常发于外周病变常发于外周全世界发病率上升全世界发病率上升高表达与小气道与免疫相关的高表达与小气道与免疫相关的基因编码蛋白

4、基因编码蛋白k-ras 突变常见突变常见支气管肺泡癌是其一个亚型支气管肺泡癌是其一个亚型大细胞肺癌大细胞肺癌 (10-25%)原始的、未分化细胞原始的、未分化细胞病变常发于外周病变常发于外周l 高度转移倾向高度转移倾向肺癌的内科治疗8nsclc 分期分期淋巴结淋巴结主支气管主支气管对侧淋巴结对侧淋巴结远处器官转移远处器官转移胸壁侵犯胸壁侵犯 iv 期期 0 期期 ia 期期 iib 期期 iiib 期期肺癌的内科治疗9 nsclc:nsclc: 分期及生存分期及生存mountain. chest. 1997;1710-1717.stage i stage ii stage iii stage

5、iv020406080100percent survivorsstage at diagnosisst ist iist iiiast iiibst iv肺癌的内科治疗10肺癌肺癌内科治疗研究进展内科治疗研究进展肺癌的内科治疗11肺癌的内科治疗12nsclcnsclc：复发形式复发形式肺癌的内科治疗13背景背景肺癌的内科治疗14ialtialt临床研究设计临床研究设计rchemotherapycontrol thoracic radiotherapy thoracic radiotherapy 60 gy 60 gy* * *optional, but predefined by n stag

6、e at each centeroptional, but predefined by n stage at each center 完全切除完全切除 nsclcnsclc asco, chicago, june 2, 2003asco, chicago, june 2, 2003肺癌的内科治疗15 化疗方案化疗方案肺癌的内科治疗16 结结 果果化疗化疗对照对照 n 932935 中位生存期中位生存期50.8 months44.4 months 中位无病生存期中位无病生存期40.2 months30.5 months 5-年生存率年生存率44.5 %40.4 % 5-年年无病生存率无病生存率3

7、9.4 %34.3 %肺癌的内科治疗170%20%40%60%80%100%012345hr= 0.86 0.76-0.98 p0.03总生存期总生存期controlchemotherapy years164286432602774935181308450624775932at risk 肺癌的内科治疗180%20%40%60%80%100%012345hr= 0.83 0.74-0.94 p0.003无病生存无病生存controlchemotherapy years141244365505655935158272397544684932at risk 肺癌的内科治疗19 总总 结结 5年总生

8、存率提高年总生存率提高4.1% （ 40.4% vs 44.5%） p0.03 5年无病生存提高年无病生存提高5.1 % ( 34.3% vs 39.4%，p0.003) 致死性毒性致死性毒性 0.8% 肺癌的内科治疗20correlation correlation betweenbetween stage and stage and activity of chemotherapyactivity of chemotherapy- positive - negative- not tested肺癌的内科治疗21asco 2003 ialt (le havalier)asco 2003jlc

9、rg (kato)asco 2004jbr 10 (winton)asco 2004calgb (strauss)肺癌的内科治疗22有待解决的问题有待解决的问题肺癌的内科治疗23选择哪些患者？选择哪些患者？肺癌的内科治疗24化疗的时机？化疗的时机？化疗周期？化疗周期？肺癌的内科治疗25 新辅助治疗新辅助治疗肺癌的内科治疗26nsurvivalmedian(mo)2-ys%rosell*chemo+surg302632surg alone3080roth*chemo+surg286460surg alone321125*nejm,1994 *jnci86;1994肺癌的内科治疗27新辅助治疗新辅

10、助治疗：swog 9900swog 9900 泰素泰素 225 mg/m2卡铂卡铂 auc = 6x 3 cycles 手术手术randomize手术手术stage ib, ii and iiia (t3n1) n= 374/600primary endpoint: 33% improvement in the expected 2.7 medians survival for surgery alonepisters k, et alasco abstract # 7012:肺癌的内科治疗28无疾病进展生存期无疾病进展生存期hr=0.80 0.59-1.07, p=0.140%20%40%6

11、0%80%100%01224364860months after registrationmedian1 yr2 yrpreop31 mo69%55%control20 mo68%46%median f/u 31 mo swog 9900 swog 9900肺癌的内科治疗29总生存总生存 hr=0.84 0.60-1.18, p=0.320%20%40%60%80%100%01224364860months after registration swog 9900swog 9900median 1 yr 2 yrpreop47 mo 82%69% control40 mo 79%63%medi

12、an fu 31 months肺癌的内科治疗30cisplatin, 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疾病无进展者疾病无进展者 手术手术继续放疗至继续放疗至 61 gy61 gy 巩固化疗巩固化疗cisplatin plus etoposidex 2 cycles诱导治疗诱导治疗albain ks et al肺癌的内科治疗31ct/rt/s 145/202ct/rt 155/194logrank p = 0.24hazard

13、 ratio = 0.87 (0.70, 1.10)% alive0255075100months from randomization01224364860dead/total overall survivalmedian fu 81 months肺癌的内科治疗32 overall survival by pathologic nodal overall survival by pathologic nodal statusstatusno surgery (n=38)pathologic n0 (n=76)pathologic n1-3, unknown (n=88)p 0.0001% a

14、live0255075100months from randomization020406080100120肺癌的内科治疗33 肺叶切除的总生存肺叶切除的总生存subset vs matched ct/rt subset % alive0255075100months from randomization01224364860/ / / / / / / / /logrank p = 0.002ct/rt/s 57/90ct/rt 74/90dead/totalms 34 mos. 22 mos.5 yr os 36% 18%ct/rt/s ct/rt肺癌的内科治疗34months from r

15、andomization全肺切除的总生存全肺切除的总生存subset vs matched ct/rt subset ms3 yr os5 yr os19 mos. 36% 22%ct/rt/sct/rt% alive025507510001224364860/29 mos. 45% 24%dead/totalct/rt/s38/51ct/rt42/51logrank p = ns肺癌的内科治疗35n2 病人是否外科治疗需肺癌多学科讨论决定病人是否外科治疗需肺癌多学科讨论决定 肺癌的内科治疗36肺癌的内科治疗372005 nccn2005 nccn临床肿瘤指南临床肿瘤指南多学科治疗：辅助化疗多

16、学科治疗：辅助化疗肺癌的内科治疗382005 nccn2005 nccn临床肿瘤指南临床肿瘤指南多学科治疗：辅助化疗多学科治疗：辅助化疗肺癌的内科治疗39术后辅助化疗术后辅助化疗肺癌的内科治疗40肺癌肺癌内科治疗研究进展内科治疗研究进展肺癌的内科治疗41 不能手术局部晚期不能手术局部晚期nsclcnsclc化化放疗结合的方式放疗结合的方式肺癌的内科治疗42 lamp: randomized phase ii study of 3 lamp: randomized phase ii study of 3 chemoradiation schedules for stage iii chemora

17、diation schedules for stage iii nsclcnsclc 肺癌的内科治疗43lamp: pre-treatment characteristicslamp: pre-treatment characteristics肺癌的内科治疗44t/crthistorical 1 yr 59% 58%2 yr 31% 31%median 13.0 mo 14.5t/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%

18、 31%median 16.1mo 14.5mo_-arm 1arm 3arm 2肺癌的内科治疗45 swog 9504: treatmentswog 9504: treatmentconcurrent 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-

19、100 mg/m2 iv x 2 cycles(every 3 weeks)gaspar le, et al. proc am soc clin oncol 2001;20:315a. (abstr & poster 1255) 肺癌的内科治疗46phase ii swog trial (s9504): resultsradiographic response n= 83 complete response 3 (4%) partial response 49 (59%) overall response 52 (63%) stable disease 23 (28%) disease

20、 progression 8 (9%) survival median27 mos 18 - 43 mos 1-year survival76% 67% - 85% 2-year survival54% 43% - 64% 3-year survival40% 24% - 55%肺癌的内科治疗47肺癌的内科治疗48swog 9504overall survival0%0%20%20%40%40%60%60%80%80%0 01212242436364848months months registration registrationmedianmediann n in months in mo

21、nths83 4583 45 26 261 year survival: 76%1 year survival: 76%2 year survival: 54%2 year survival: 54%3 year survival: 40%3 year survival: 40%gaspar: asco 2001肺癌的内科治疗49 swog 9504 (pe/rt swog 9504 (pe/rt txt) txt) vs swog 9019 (vs swog 9019 (pe/rt pe/rt pe) pe): : patient characteristics patient charac

22、teristics肺癌的内科治疗50 swog 9504 (pe/rt swog 9504 (pe/rt txt) txt) vs swog 9019 (vs swog 9019 (pe/rt pe/rt pe) pe): : survival (median f/u 28 mos) survival (median f/u 28 mos) 3 year 40% 24-55 3 year 40% 24-55 17% 7-27 17% 7-27 4 year 39% 4 year 39% 17%17%gaspar le, et al. proc am soc clin oncol 2001;20

23、:315a. (abstr & poster 1255) 肺癌的内科治疗51current status of chemoradiotherapy in current status of chemoradiotherapy in stage iii nsclcstage iii nsclc adapted from pisters: asco, 2000 * s9504肺癌的内科治疗522005 nccn临床肿瘤指南多学科治疗：辅助化疗肺癌的内科治疗53肺癌肺癌内科治疗研究进展内科治疗研究进展肺癌的内科治疗54 治疗原则治疗原则肺癌的内科治疗55联合化疗作为联合化疗作为nsclcns

24、clc的一线治疗的一线治疗肺癌的内科治疗56advanced nsclcadvanced nsclcus fda approved therapiesus fda approved therapieschemotherapy)chemotherapy)肺癌的内科治疗57 nsclc: nsclc: 一线化疗一线化疗肺癌的内科治疗58 治治 疗疗长春瑞滨长春瑞滨 30 mg/m30 mg/m2 2，第，第1 1、8 8天天 每每3 3周周 + + 最佳支持治疗最佳支持治疗最佳支持最佳支持治疗治疗 (bsc)紫杉醇紫杉醇 200 mg/m200 mg/m2 2 第第1 1天天 每每3 3周周 +

25、bsc + bsc最佳支持治疗最佳支持治疗泰索帝泰索帝 100 mg/m100 mg/m2 2 第第1 1天天 每每3 3周周 + bsc + bsc最佳支持治疗最佳支持治疗吉西他滨吉西他滨 1000 mg/m 1000 mg/m2 2 第第1 1、8 8和和1515天天 每每4 4周周 + bsc + bsc最佳支持治疗最佳支持治疗肺癌的内科治疗591.00.80.60.40.2003691215182124长春瑞滨长春瑞滨最佳支持治疗最佳支持治疗月月概率概率肺癌的内科治疗601.00.80.60.40.2003691215182124紫杉醇紫杉醇最佳支持治疗最佳支持治疗月月概率概率肺癌的内

26、科治疗611.00.80.60.40.2003691215182124泰索帝泰索帝最佳支持治疗最佳支持治疗月月概率概率肺癌的内科治疗621.00.80.60.40.2003691215182124吉西他滨吉西他滨最佳支持治疗最佳支持治疗月月概率概率肺癌的内科治疗63ecog 1594: study designecog 1594: study designstratification:ustage: iiib vs ivups: 01 vs 2uwt loss: 5% vs 5%ucns mets: no vs yesarm aarm a: cisplatin + paclitaxel: ci

27、splatin + paclitaxelpaclitaxel: 135 mg/mpaclitaxel: 135 mg/m2 2/24 h day 1/24 h day 1 cisplatin: 75 mg/m cisplatin: 75 mg/m2 2 day 2 day 2q3wkq3wkarm darm d: carboplatin + paclitaxel: carboplatin + paclitaxelpaclitaxel: 225 mg/mpaclitaxel: 225 mg/m2 2/3 h day 1/3 h day 1carboplatin: auc 6 day 1carbo

28、platin: auc 6 day 1arm carm c: cisplatin + docetaxel: cisplatin + docetaxeldocetaxel: 75 mg/mdocetaxel: 75 mg/m2 2 day 1 day 1cisplatin: 75 mg/mcisplatin: 75 mg/m2 2 day 1 day 1arm barm b: cisplatin + gemcitabine: cisplatin + gemcitabinegemcitabine: 1000 mg/mgemcitabine: 1000 mg/m2 2 days 1, 8, 15 d

29、ays 1, 8, 15cisplatin: 100 mg/mcisplatin: 100 mg/m2 2 day 1 day 1q4wkq4wkq3wkq3wkq3wkq3wkschiller 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 ra an nd do ommi iz ze e肺癌的内科治疗64e1594 肺癌的内科治疗65ecog 1594:analysis of ecog 1594:analysis of t

30、oxicitytoxicity222266667 7626211115656272728280 010102020303040405050606070703 3 级级4 4 级级%泰素泰素/ /顺铂顺铂吉西他滨吉西他滨/ /顺铂顺铂多西紫杉多西紫杉醇醇/ /顺铂顺铂泰素泰素/ /卡铂卡铂psps2 2的病人的的病人的3-43-4级毒性发生百分比级毒性发生百分比肺癌的内科治疗66 tax326 study design tax326 study design （泰素蒂铂类泰素蒂铂类vs nvb+vs nvb+铂类铂类）randomizestratifiication factors: stage

31、 of diseaseiiib vs. ivand regionus/canada south americaeurope/lebanonisraelsouthafrica/australianew zealandresponse assessment every 2 cycles泰素蒂泰素蒂 75mg/m2 iv 卡铂卡铂 auc 6 iv q 3 wks(tcb)诺维苯诺维苯 25mg/m2 iv d 1, 8, 15 & 22顺铂顺铂 100mg/m2 iv d 1q 4 wks(vc)泰素蒂泰素蒂 75mg/m2 iv顺铂顺铂 75mg/m2 iv q 3 wks（tc）vs.

32、or肺癌的内科治疗67 tax 326 overall tax 326 overall survivalsurvivalfossella et al. j clin.oncol. 2003;21:3016-3024.100806040200survival (%)0369 12 15 18 21 24 27 30 33time (months)tcvc100806040200survival (%)036912 15 18 21 24 27 30 33time (months)p = .657, adjustedlog-rank testtcbvc1-y survival 46% vs 41%

33、 with vc2-y survival 21% vs 14% with vcmedian survival: 11.3 vs 10.1 mop = .044, adjusted log-rank test1-y survival 38% vs 40% with vc2-y survival 18% vs 14% with vc肺癌的内科治疗68randomizeprotocol schemastratification weight loss in previous 6 months: 5% vs 5% disease stage: iiib with effusion, iv brain

34、metastases: presence or absencegemcitabine 1000 mg/m2 d 1,8paclitaxel 200 mg/m2 d 1q 21 daysgemcitabine 1000 mg/m2 d 1,8carboplatin auc 5.5 d 1q 21 daysarm a: 健择健择 + 卡铂卡铂arm b: 健择健择+ 泰素泰素arm c: 泰素泰素+ 卡铂卡铂paclitaxel 225 mg/m2 d 1carboplatin auc 6.0 d 1q 21 days肺癌的内科治疗69survival by treatment arm肺癌的内科治

35、疗7090年代新化疗药物联合作为非铂方案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卡铂卡铂vsvs顺铂顺铂肺癌的内科治疗72nsclc: 90nsclc: 90年代新化疗药物顺铂或卡铂的随机研究年代新化疗药物顺铂或卡铂的随机研究 n zojwalla, 2004n zojwalla, 2004肺癌的内科治疗73 nsclc: nsclc: 9090年代新化疗药物顺铂或卡铂的随机研究年代新化疗药物顺铂或卡铂的随机研究 n zojwalla, 2004n zojwalla,

36、 2004months carboplatin cisplatin n = 1152 n = 11548.79.8* no other such trials 1992 2003; * 2 trials with paclitaxel, 1 with docetaxel, 2 with gem. 肺癌的内科治疗74copyright american society of clinical oncologycarbo vs. cis meta-analysiscarbo vs. cis meta-analysisoverall survival with cisplatin-based com

37、pared overall survival with cisplatin-based compared with carboplatin-based chemotherapywith carboplatin-based chemotherapyhotta, k. et al. j clin oncol; 22:3852-3859 2004肺癌的内科治疗75copyright american society of clinical oncologycarbo vs. cis meta-analysiscarbo vs. cis meta-analysisoverall survival wi

38、th cisplatin plus new agents overall survival with cisplatin plus new agents compared with carboplatin plus new agentscompared with carboplatin plus new agentshotta, k. et al. j clin oncol; 22:3852-3859 2004肺癌的内科治疗76一线化疗一线化疗: : 怎样选择最好的联合方案怎样选择最好的联合方案? ? 疗效与生存疗效与生存? ? 生活质量生活质量? ? 毒性毒性? ? 病人的基础状态病人的基础

39、状态? ? 费用费用? ?肺癌的内科治疗77weekly paclitaxel with carboplatin followed by maintenance paclitaxel vs.observation for advanced nsclc 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 paclitaxel with carboplatin followed by main

40、tenance paclitaxel vs.observation for advanced nsclcefficacy/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%t

41、hrombocytopenia 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79stratifyecog ps0&1 vs 2stageiiib vs ivrandomizeweeklypaclitaxel 100 mg/m2/week x 3carboplatin auc=6 (cycle duration 4 weeks, total 4 cycles)standardpaclitaxel 225 mg/m2 3carboplatin auc= 6 day

42、 1 (cycle duration 3 weeks, total 4 cycles)taxmen 12 : phase iii study schema*maintenance 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肺癌的内科治疗80taxmen 12: kaplan-meier estimates patient survival1.00.90.80.70.60.50.40.30.

43、20.10.0081624324048566472808896104112 120 128 136 144 152 160weeklystandardproportion of patients who survivedtime (weeks)肺癌的内科治疗81肺癌的内科治疗82with mt vs. 49.6 wks without mt, p = 0.016)-role?ncan this concept be validated with other agents?肺癌的内科治疗83combination in select patients with non-squamous carc

44、inoma metastatic lung cancer肺癌的内科治疗84fda fda 批准的批准的nsclcnsclc二线治疗药物二线治疗药物docetaxeldocetaxelpemetrexedpemetrexederlotiniberlotinib肺癌的内科治疗85nsclcnsclc 二线治疗：泰素蒂二线治疗：泰素蒂 vs bsc shepherd et al 2000中位生存期中位生存期(月月)1年年 生存率生存率(%)log rank: p=0.01泰素蒂泰素蒂 75 mg/m2 (n=55)最好的支持治疗最好的支持治疗 (n=49)036912151821累计的概率累计的概率

45、0.00.20.40.60.81.0泰素蒂泰素蒂75 mg/m27.537最好的支持最好的支持治疗治疗4.612月月肺癌的内科治疗86% pemetrexed n = 265 泰索帝 n = 276 泰索帝 n=100(q3 week) n=98 (weekly) alt 升高 2 0 n/a 虚弱 5 5 n/a n/a grade3/4 中性粒细胞减少 5 40 8.8 2.3 粒缺性发热 2 13 1.1 1.1 grade 3/4 贫血 4 4 3.3 5.7 grade 3/4 血小板减少 2 2 (ideal 2)previouschemotherapyregimenscontin

46、ue gefitinib until diseaseprogression or unacceptable toxicityprimary endpointspatientsl response rate (both trials)l safety profile (ideal 1)l symptom relief (ideal 2)ideal 1 global trial including japan, europe, australia, and south africa (jpn=209)ideal 2 usa trialnatale & zaretsky 2002 rando

47、mizeddrandomizedd肺癌的内科治疗93gefitinib (iressa)gefitinib (iressa)治疗晚期治疗晚期nsclcnsclc的研究的研究( (ideal-1,2)ideal-1,2)肺癌的内科治疗94gefitinibgefitinib作为三线药物治疗作为三线药物治疗晚期晚期nsclcnsclc的研究的研究semin oncol. 2003;30(1 suppl 1):30-85154疾病控制率疾病控制率()1918有效率（）有效率（）500mg/d250mg/dideal-1n2103543症状改善率症状改善率()912有效率（）有效率（）500mg/d2

48、50mg/dideal- 2n216肺癌的内科治疗95gefitinibgefitinib作为三线药物治疗作为三线药物治疗晚期晚期nsclcnsclc的的期研究期研究oncologist. 2003;8(4):303-6. 7.04.58.9中位有效期(月)10.67.913.6有效率（）两组合并(n=142)500mg/d (n=76)250mg/d(n=66)结论：结论：gefitinibgefitinib用于铂类和多西紫杉醇治疗失败的晚用于铂类和多西紫杉醇治疗失败的晚期期nsclcnsclc病人，推荐结论是病人，推荐结论是250250mg/dmg/d。因为因为500500mg/dmg/d

49、的疗的疗效无增加，但毒性更大。效无增加，但毒性更大。肺癌的内科治疗96isel:iressa survival isel:iressa survival evaluation in lung cancer evaluation in lung cancer (trial 709)(trial 709)肺癌的内科治疗97isel：bankground肺癌的内科治疗98iressa(250 mg/day) 1 end-pointsurvival2 end-pointsttforrqol, symptomssafetyexploratory end-pointtumour biomarker ana

50、lysis (eg egfr)placebo + bscct, chemotherapy; bsc, best supportive care; egfr, epidermal growth factor receptor; ttf, time to treatment failure; orr, objective response rate; qol, quality of lifepatientslocally advanced or metastatic nsclc1 or 2 prior ct regimensintolerant to most recent ct regimen

51、or progression 90 days of last ct cycleisel trial design肺癌的内科治疗990246810121416time (months)at risk:1692134787748525210431median, months1-year survival, %logrank hr (95% ci), 0.89 (0.77, 1.02); p=0.087cox regression analysis, p=0.030iressa5.627placebo5.1210.00.20.40.60.81.0proportionsurvivingiressapl

52、aceboci, confidence interval; hr, hazard ratiomedian follow-up: 7 months (range 315); 58% deathsisel: survival in the overall population肺癌的内科治疗100median, months1-year survival, %logrank hr (95% ci), 0.84 (0.68, 1.03); p=0.089cox regression analysis, p=0.033iressa6.330placebo5.418time (months)at risk

53、:81266944626214566181iressaplacebo02468101214160.00.20.40.60.81.0proportionsurvivingisel: survival in the adenocarcinoma population肺癌的内科治疗101169210515392781294917iressaplaceboiressaplacebocox analysis (95% ci)logrankodds ratio (95% ci)median ttf, months3.02.60.82 (0.73, 0.92) p=0.0006p=0.002orr, % (

54、n)8.0 (77/959)1.3 (6/480)7.28 (3.1, 16.9)p0.0001ttf (months)at risk:02468101214160.00.20.40.60.81.0proportionwithout treatment failureisel: significant improvement in ttf and orr肺癌的内科治疗102reasons for treatment failurepatients (%)iressaplacebo6050403020100肺癌的内科治疗103overall response rate11%women18%men

55、5%never smokers29%current/former5%smokersadenocarcinoma12%other nsclc7%肺癌的内科治疗104lynch:nejm2004肺癌的内科治疗105 ggcgggccaaactgctgggtgcg 100selection of patients for egfr inhibitors肺癌的内科治疗106 5/5 patients who responded to gefitinib had egfr mutations 4/4 patients who progressed on gefitinib had no egfr mut

56、ationspaez: science express rep 2004.characteristicadenocarcinoma other nsclcfemale malejapaneseamerican% with mutation (n) 21% (15/70) 2% (1/49)20% (1/45)9% (7/74)26% (15/58)2% (1/61)肺癌的内科治疗107is a bath and a shower always better than either alone?肺癌的内科治疗108肺癌的内科治疗109ecog trial (e4599): rhumab vegf

57、 (ecog trial (e4599): rhumab vegf (贝伐单抗贝伐单抗bevacizumab) bevacizumab) 在晚期在晚期nsclc (non-squamous)nsclc (non-squamous)sample size of 842 patients for 80% power to detect a 25% improvement in median survival ( 8 to 10 mos.)肺癌的内科治疗110病人特点病人特点 (eligible patients)肺癌的内科治疗111非血液学毒性非血液学毒性肺癌的内科治疗1120.00.20.40.

58、60.81.0progression-free survival by treatmentprobabilitypcpcbp 0.0001061218243036monthsmedians: 4.5, 6.46 mo. 1 yr33% 6%55%15%ecog trial (e4599): rhumab vegf (bevacizumab) in ecog trial (e4599): rhumab vegf (bevacizumab) in advanced nsclc (non-squamous)advanced nsclc (non-squamous)肺癌的内科治疗1130.00.20.40.60.81.0survival by treatmentprobabilitypcpcb