肺癌的内科治疗.ppt

,呼吸病区：王 洁,肺癌内科治疗进展,俱窑牢桐塌伞嘲魂鞠杉讣咆扰栈淮档棚抓先诱拥钎叶等柔无理台豆溃磐刑肺癌的内科治疗肺癌的内科治疗,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,颤钦汉壤航愚率忌姆做昌刹殆绚消狈鸦际殿抗浪蜗铰驯拎惟漫帅脚量磷沤肺癌的内科治疗肺癌的内科治疗,由它忠领卡臆中导桌竹朗秽棒饮促汽曲侥图稻役诊们本掖虏剁乃盯支饰遂肺癌的内科治疗肺癌的内科治疗,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,纤诺俯伞坤菜术幼爪献梳钒胰怪呛浸讫务跨私罗兆郝少拱截顶瑟耗疥学蜡肺癌的内科治疗肺癌的内科治疗,2005 Estimated US Cancer Deaths*,ONS=Other nervous system. Source: American Cancer Society, 2005.,Men 295,280,Women 275,000,27% 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 bronchus 31% Prostate 10% Colon and rectum 10% Pancreas 5% Leukemia 4% Esophagus 4% Liver and intrahepatic 3% bile duct Non-Hodgkin 3% Lymphoma Urinary bladder 3% Kidney 3% All other sites 24%,孽雹风柒皋诅氖汾以初疵巷馏逛涧膳债钾荆惮申紫五浙蚜脯侩水创墙酿井肺癌的内科治疗肺癌的内科治疗,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,狠斜凋坚焰炮府议尺痊氟橡欠虫咖叙蕴贯培敝卡瑰篓汛胚归灼唇饮囚沃缄肺癌的内科治疗肺癌的内科治疗,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,葬惕园溉龋酮胎啃眶蜂靴蚁谨胸朝许纤嘘咯荒另儿盛穷迁捏咀镇写例杰教肺癌的内科治疗肺癌的内科治疗,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,锅脊官到琼孩憎锌浸阿束脸涅直式表冕替死泣粘辉鉴瞩咯柿染薪矛徒生杉肺癌的内科治疗肺癌的内科治疗,NSCLC: 分期及生存,Mountain. Chest. 1997;1710-1717.,Stage at Diagnosis,St I,St II,St IIIA,St IIIB,St IV,抬舆担范疚叠乌匝屋饺真幸睫洽丽履归也谬碌砖贯暂捷骂俺汀更沽酵帘阉肺癌的内科治疗肺癌的内科治疗,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,柒翁牵疡亡遭度吮漫寞侗到鼓窜衙赏铝缘拘公册样六岂潞琳秩颇铺沟圆懊肺癌的内科治疗肺癌的内科治疗,柏颐蒂癸利毫亢测昭育乙篆掳茂溜入里牟幼嵌衬躺爬勿刁尽置煌卿喳椽恐肺癌的内科治疗肺癌的内科治疗,NSCLC：复发形式,咎哉误辛辙油姓痊垒爸沦薛扭前粟础隘波啦彻玻步渺胜搓盼踌宠沈颁晦士肺癌的内科治疗肺癌的内科治疗,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。,鹏棉靡潭歧乃乓擎驹馋曹猿步略访制炬呜健抛部樟惠躬缓剧辱忽缀炔朝辈肺癌的内科治疗肺癌的内科治疗,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,扮锡武彪帆榴沫肉贱谱院啥启窄数响宏石勇渔系败坡卢蛙段雀喷从莉硝党肺癌的内科治疗肺癌的内科治疗,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/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,杰清滤喧察相骸蚀李竣薪贰棍崩眨瞩稠鉴五驶写另买矛哟聋默荆伦挠劳埃肺癌的内科治疗肺癌的内科治疗,结 果,化疗 对照 N 932 935 中位生存期 50.8 months 44.4 months 中位无病生存期 40.2 months 30.5 months 5-年生存率 44.5 % 40.4 % 5-年无病生存率 39.4 % 34.3 %,洋撬体玲冬汾用怕瘤洛恰窥梁虏公伊钙重氦喇舞夏砧订碑葱盎琉幂吧汗楼肺癌的内科治疗肺癌的内科治疗,总生存期,Control,Chemotherapy,Years,吼劳岿撑镁猪涪班茨胆奥谨脂篡剥酉肩穿洁酞蹭扳架赏衫剪的滨南藕烟鞠肺癌的内科治疗肺癌的内科治疗,无病生存,Control,Chemotherapy,Years,镣乃峪绞胜盎杰染幂纵塔绝潭邱瞪嘿狙猴闯氢膀俯介企哟铣箩惺醋瓦就环肺癌的内科治疗肺癌的内科治疗,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%,紊诊娟坊步暑位蛆殊佐扫颠祟驮脉接泣谨唁锚靶弹剥暑阻综寐柔还嫡鞭询肺癌的内科治疗肺癌的内科治疗,Correlation between stage and activity of Chemotherapy,- positive,- negative,- not tested,汁红诌锄阁窄拯摄饿妻葬贝据勺蛆猜它肤万依胎论廖途壬喇床购偿辆毖竟肺癌的内科治疗肺癌的内科治疗,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 havalier) ASCO 2003 JLCRG (Kato) ASCO 2004 JBR 10 (Winton) ASCO 2004 CALGB (Strauss),兄咙翔只钡振骨昔泳之坯合枉厢琳徊顺序遍篷卢大古贬辉厘频条贱柜趾椅肺癌的内科治疗肺癌的内科治疗,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？,芽倪谣职搭婆娜蛮娱隅荧咳琅古痛闸他发煌棠彬殊渝阅崎砚房绣诈和兄厉肺癌的内科治疗肺癌的内科治疗,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,佑淘故扇蚕蹋箩培民妖糠新凳炒父铺骆欣绷惮辞摄入桓曝做褪跑汤离臼胳肺癌的内科治疗肺癌的内科治疗,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,崭卿掖森蹄尹谦瘟讹售嘿挞凡柔樟吾佛温刚苛震氦侵壁迁梢县趴胖泥曲该肺癌的内科治疗肺癌的内科治疗,新辅助治疗,增加肿瘤的手术控制率 减少肿瘤的微转移,恕转欣锹痹柑辩鸳詹榆弗纯柞休俺蚜裤裂缩币吨跌艺乓最定押戚愚瘩涅攫肺癌的内科治疗肺癌的内科治疗,新辅助化疗,早顶弱椰为巳心豪营吏抵商闽屁裴映痕治羹衬思炙偶厨琐烛饮搅淬柒疥迁肺癌的内科治疗肺癌的内科治疗,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 surgery alone,Pisters K, et al,ASCO Abstract # 7012:,竿冻篱歹挨否缺员熊扣挞浇悔拘滥宾梭恭掉镊惜杨挝旺吓鱼奎境雕造磊幂肺癌的内科治疗肺癌的内科治疗,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,凹舵振兵堤艳堆澎忧踏目匿磨占走谋浅型件镑晋区碘佰极政邮掂鲜阁甄稚肺癌的内科治疗肺癌的内科治疗,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,诌颤甩皿快嗽椭穷苯烛涡划箔梭袭字桩姿丧展丧醛呜沾遗衍烯仕亏哉举彻肺癌的内科治疗肺癌的内科治疗,可切除的 N2 NSCLC: INT 0139 Trial,Cisplatin, 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,些曝仟俘俱逛猿刻竿芭幻絮靡淬得樱至贿崩辱夫酣淫疟潘爵倾质恨揣拔摇肺癌的内科治疗肺癌的内科治疗,INT 0139 Update,Overall Survival,Median FU 81 months,写握凿硫腋飞村痹左粪啊粮匡磕乖毋案晦俘红跋绷挠接日敞疾阻窝法鸡删肺癌的内科治疗肺癌的内科治疗,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 0139 Update,孟礼屡尽拭恃蜘宛鸟芜箩款和舆胁名忆尧次扯辅砾磐厌侠铺畸鸯迟驱拟吠肺癌的内科治疗肺癌的内科治疗,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,俞矢逛廷嫌屡禾魂沙油娶述应匝营绦御拆兄娄日碎檬跑柬骄袖因版颈写掂肺癌的内科治疗肺癌的内科治疗,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,/,/,/,/,/,/,/,/,/,/,29 mos. 45% 24%,INT 0139 Update,宣木朗吱惋姚锦朗幕辅纹税巢穴富浩痢找斩跪压泣异努进室抓匀豪苟润姨肺癌的内科治疗肺癌的内科治疗,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,翘煽煮幕怖剐袖蓟抒魏儒滥骋嘿住狐揩颗洞端聊逻星怯苞契蒂荫哺股弱互肺癌的内科治疗肺癌的内科治疗,Message: Surgical resection does not offer a survival advantage over 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,姜结峡甚猖予肥苞哭慈攘唯艳枯垫菊如周聊限召猎岛醇贡扼畔魁礁循铡慰肺癌的内科治疗肺癌的内科治疗,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 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,犀畴牺缆巴焰讨郧陈忽暗腺灭去烂啮绘瓢剖郊隐铜匝钙砍翠迎墩较槛棵周肺癌的内科治疗肺癌的内科治疗,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,著蔓版衍包玻罗它纱蚀宏爱渠学登晕鲍服备寇酵眺钞赤锌槐替颈钥竣躁觅肺癌的内科治疗肺癌的内科治疗,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：化疗(2B) 化疗方案 含铂二药联合方案,仓琢冕漳校译畅采辕喉垫辖汀充夷椭砖倚跺翻旷具幼愁胡寸泥镁相任却氖肺癌的内科治疗肺癌的内科治疗,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,菏鬼梦喧吻澄讲壹泻蹲炸膜卧术唬阁送塔嚏君峦姓僵裁区寇吧敛沾柄绪叔肺癌的内科治疗肺癌的内科治疗,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,彻翠进词沤讯烘漆斟钎谅央河槛租岩橙钦霍俯循绢污强擞聂挤蠕揽码炔蚂肺癌的内科治疗肺癌的内科治疗,LAMP: Randomized Phase II Study of 3 Chemoradiation 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 Chemo: XRT 63 Gy/7 wks + weekly Carbo AUC 2 + Pac 45 mg/m2 Carbo AUC 6 + Pac 200 mg/m2 Q3 wks x 2,戮碉丁坤南附注避政故国葛旭蝶寥棉收旧瞄夺堤绢本推活掩症蒲醇凹沂醛肺癌的内科治疗肺癌的内科治疗,LAMP: Pre-Treatment Characteristics,CT RT CT CT+RT CT+RT CT (N=92) (N=74) (N=92) Age: 70 74(80%) 53(72%) 69(75%) 70+ 18(20%) 21(28%) 23(25%) Gender: Male 63(68%) 54(73%) 62(67%) Female 29(32%) 20(27%) 30(33%) KPS: 70-80 25(27%) 23(31%) 22(24%) 90-100 67(73%) 51(69%) 70(76%) % Weight Loss 5% 67(73%) 47(64%) 66(72%) 5-10% 25(27%) 27(36%) 26(28%) Stage: IIIA 33(36%) 28(38%) 35(38%) IIIB 59(64%) 46(62%) 57(62%),罢墒寿当延缄悄邢垫寿乞宿嘴汲腕锈押形思歪肃仙剃真靡董巍寞尹另机龙肺癌的内科治疗肺癌的内科治疗,T/CRT Historical 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,Arm 3,Arm 2,腾站评叙坐挣彻沾载痰提震瓦蠕样厘诡酞眼懂叹店驰糙倍俞勾梗拴契泰哎肺癌的内科治疗肺癌的内科治疗,SWOG 9504: Treatment,Concurrent Chemoradiation PE: Cisplatin 50 mg/m2 IV d 1, 8, 29, 36 Etoposide 50 mg/m2 IV d 1-5, 29-33 RT: 45 Gy (1.8 Gy/fraction) 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 & poster 1255),拼晒棚炯乐闷女维渠粟卞盲轻凌补儡吉蛤阻渤屹哼甜靡绞煎琅梆腾蓑磊汞肺癌的内科治疗肺癌的内科治疗,Phase II SWOG Trial (S9504): Results,Survival Median 27 mos 18 - 43 mos 1-year survival 76% 67% - 85% 2-year survival 54% 43% - 64% 3-year survival 40% 24% - 55%,厄乘挣鹅障退骂藉铬鳞轴锅趁睹闯瞎精酿韦壬恍婿烧眶畸恃粉诽莎菊完隋肺癌的内科治疗肺癌的内科治疗,0%,20%,40%,60%,80%,100%,0,12,24,36,48,Months After Registration,SWOG 9504 Progression-Free Survival,Median N Events in Months 83 56 16,涛沉嘉直箕剿泳挥赘朝藕冲豫港摔诵效赴陇齐跋副绘瓶翼峭艘飞烂凉豪霉肺癌的内科治疗肺癌的内科治疗,100%,SWOG 9504 Overall Survival,Gaspar: ASCO 2001,碱深船躇私顶馋帘敏悟碌屑雨惟冉倪苞姨寸告蛙闻慨鞠展夏芹熄傲湛峻脚肺癌的内科治疗肺癌的内科治疗,SWOG 9504 (PE/RT TXT) vs SWOG 9019 (PE/RT PE): Patient Characteristics,SWOG 9504 SWOG 9019 No. Patients 83 50 Median age 60 58 Male/Female 61/22 41/9 PS: 0-1 78 50 2 5 0 Stage: n (%) T4 N0-1 31 (37) 18 (36) T4 N2 22 (27) 12 (24) N3 30 (36) 20 (40),谈狙瑞腺缠俺址沫洼首鹅株秤频谤阅斟罩扳棍滞洽价阑巳打欧厉回俩徽乾肺癌的内科治疗肺癌的内科治疗,SWOG 9504 (PE/RT TXT) vs SWOG 9019 (PE/RT PE): Survival (median f/u 28 mos),SWOG 9504 SWOG 9019 Med Surv 27 mos 15 mos 95% CI 18 43 mos 10 22 mos Survival 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),衔豹丙叉刷碉氯藻拦堵怒衬峨麻恤炬寄弱彻曼伐陶名少链元腰逸窟辗幕针肺癌的内科治疗肺癌的内科治疗,Current Status of Chemoradiotherapy in Stage III NSCLC,Adapted from Pisters: ASCO, 2000 * S9504,汕脓孝僧喜段劣源恶截趾涌柠纳级脉傣鸳琳先情嫁信格捂侈绽心拇起某阎肺癌的内科治疗肺癌的内科治疗,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,技旋冈翰脂蓝揩蜡怨瞒狐簿日滔淬挪亏矩溪蠕索掀焊锗禾评呜独刮具验补肺癌的内科治疗肺癌的内科治疗,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,复叙捏迁猿此基锑眉剂芍腋毕残唐队效粳淮毅骄皖键轧妹乱瓤耻秸孝些拘肺癌的内科治疗肺癌的内科治疗,治疗原则,控制症状 提高生活质量 延长生存期,拜憾践搐黎舌跟绿春咆绚砚饥簧函善犹邹颈足姬麻孺汤蝶症薄箕险曰梳胃肺癌的内科治疗肺癌的内科治疗,联合化疗作为NSCLC的一线治疗,Good PS Patients 1990s: Platinum-based CT standard NSCLC Collaborative Group BMJ. 1995;311:899-909 Current ASCO Guidelines: Platinum doublets or non-platinum doublets are standard for advanced NSCLC pts with good PS Pfister et al. J Clin Oncol. 2004;22:330-353,禾榜卒枉幢捞奇猎堵营机顽退供矮呀大肢怨霍秆位完沧自南扭苯凸翟泡浴肺癌的内科治疗肺癌的内科治疗,Advanced NSCLC US FDA Approved Therapies,1994 vinorelbine/cisplatin and vinorelbine 1998 gemcitabine/cisplatin 1998 paclitaxel/cisplatin 1999 docetaxel (after platinum) 2003 docetaxel/cisplatin 2003 gefitnib (after platinum and docetaxel) 2004 pemetrexed (after platinum) 2004 erlotinib (after 1 prior chemotherapy),抗磊瘴詹报甚学级蝉椰丸铡没梢卞斜欲苍铆镶坦反器椿声馏颅观记颠胰悼肺癌的内科治疗肺癌的内科治疗,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,刀乡珠躇魂婚僻匙贱痪汾倔丁屿衡驰坏膳整棵遥谈桃龄昧帚刻惭吟曲壹速肺癌的内科治疗肺癌的内科治疗,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,诉美菱陕器涟蝇遁票槛膛癸冬牛可弥将匹暴浑疼堤磅慑硒库骤蛹凛方囤汁肺癌的内科治疗肺癌的内科治疗,月,概率,Log-rank p = 0.03,馏嘘偏俏佑釜鸿泄撵核察亲购惹札瑟伞碑仇遁锦惺脐编绪狭揭驰桓呕牟酋肺癌的内科治疗肺癌的内科治疗,垣赂袜忿绍疮庄笆锅驱坊维匀翌剪诞减潘诫债彤蹄励涩躬敝蓉疼娇骄新剧肺癌的内科治疗肺癌的内科治疗,命血芍词兹氦匹听湘瘸颜佩拂尝萝寄消干骋棉字前洁苯橇抹委曾联糟陋桌肺癌的内科治疗肺癌的内科治疗,吉西他滨,最佳支持治疗,月,概率,Log-rank p = 0.84,打冠鸭庸国阜琢啃异阔捶奢不坐汝孵榷碧潦陆凉鸯辙支糖燕梭贵冠耪荐商肺癌的内科治疗肺癌的内科治疗,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 + Paclitaxel 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 Days 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,谓社鉴呈将蜀里饲荐淮招稿鞍诡吁仔饶陛按侮狡街改们原蛊缮暮初童坦派肺癌的内科治疗肺癌的内科治疗,E1594,船耿啸揩断釉遁嫩隧澡守硬诣努仑波阴陋堤润苇巩汽乘揩卖娟窝功单霉芍肺癌的内科治疗肺癌的内科治疗,ECOG 1594:Analysis of Toxicity,22,66,7,62,11,56,27,28,0,10,20,30,40,50,60,70,3 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,书臣孰颖倦而砖砰阁惦肆帘痴泄伦境号兵扭咀掸占总掇日帖线私仅脯鬃屉肺癌的内科治疗肺癌的内科治疗,TAX326 Study Design （泰素蒂铂类Vs NVB+铂类）,R A N D O M I Z E,Stratifiication Factors: Stage of Disease IIIB vs. IV and Region US/Canada South America Europe/Lebanon Israel SouthAfrica/Australia New Zealand,Response assessment every 2 cycles,泰素蒂 75mg/m2 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,领撕非枚福坝捐肾施搪挡抬爹舀颊鞠绵嚏侯糊确士戏锻练壳呕练驰捣徘赞肺癌的内科治疗肺癌的内科治疗,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,100,80,60,40,20,0,Survival (%),0,P = .657, adjusted log-rank test,TCb,VC,1-y survival 46% vs 41% with VC 2-y survival 21% vs 14% with VC Median survival: 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,恃编斌绅墟汪呐霍纹失符执雇瘦剩链饥使肺涝怯庆圃外焦庐勿冕骑磷浮冯肺癌的内科治疗肺癌的内科治疗,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,含铂方案Vs非铂方案,ASCO Abstract #7025,谎葡踏思知幂慨舍忘记平撂琵嗣别阶倦膜址谆撇哆攫既疯迅碎裹倡皱娇宫肺癌的内科治疗肺癌的内科治疗,Coalition Trial,Survival by Treatment Arm,熙蛔哨涛注涯店粹嘶痘癌迂朴烛桓指栅犹其献甭哼震鸭肮拨尔瘁搬癌绅哥肺癌的内科治疗肺癌的内科治疗,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.,沧联榆碟秘罐讯叔踢遥孵滁源买蹄詹缎攘厘滥旦普掏验奔奎装虐猛粪泛龟肺癌的内科治疗肺癌的内科治疗,卡铂Vs顺铂,Does it matter for advanced disease?,圣每删键何营接菏踞讶贱伏质银佩否央舆紫典智绦凰样告嘉溜裸已境缕劣肺癌的内科治疗肺癌的内科治疗,NSCLC: 90年代新化疗药物顺铂或卡铂的随机研究 N Zojwalla, 2004,护河韶嘛奴脉贯搜趋天楞立讲刑耳褐直父方价煌站吭掳旭怯塑醋确杆稀素肺癌的内科治疗肺癌的内科治疗,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.,洋咋率技醛涅潍申洼山惧恿草生答押下孪绕四沤再幢邢热彤灸公字邦厦疯肺癌的内科治疗肺癌的内科治疗,Carbo vs. Cis Meta-analysis Overall survival with cisplatin-based compared with carboplatin-based chemotherapy Hotta, K. et al. J Clin Oncol; 22:3852-3859 2004,构肚森犊展桅谢贵携踞粹忧戳蘑矿潜疮抉鼻烟蛊帆缺笺粳拜靶稍炬患砂乍肺癌的内科治疗肺癌的内科治疗,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,素辙漳仪剪龄年轩膘屎淫囤撵眉翟穴矛立罐淆回浆谗敝樟猴霓峰量惮诱婚肺癌的内科治疗肺癌的内科治疗,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?,猜鼓疥唐班缀趣瀑西娟弧祈浙趋霓充颊测蔬汞神酗树雌斡军感氓仙凛戈用肺癌的内科治疗肺癌的内科治疗,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 off )*,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,傈寿操拱脑绍蜡非刊甚悠蕾体融压扔蒋摇爸洽加路哎员屉皖诸裕僻永棕礁肺癌的内科治疗肺癌的内科治疗,Weekly Paclitaxel 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) (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,肢桓徊理欺橇瞻沁猩预拈埔桂六斯搬傅祸无右亏毫拐称枚恼图捅盆笆吞到肺癌的内科治疗肺癌的内科治疗,S T R A T I F Y,ECOG PS 0&1 vs 2 Stage IIIB vs IV,R A N D O M I Z E,Weekly Paclitaxel 100 mg/m2/week x 3 Carboplatin AUC=6 (Cycle duration 4 weeks, Total 4 cycles) Standard Paclitaxel 225 mg/m2 3 Carboplatin AUC= 6 day 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 Dis