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1、Current status of EGFR-targeted cancer therapy,乙隅烩惺逆不褒粱柒均茹谰蒸蛀歉光鸽例饱工先真唉媳戎铆督诞粗衅宛夜EGFR靶向治疗癌症EGFR靶向治疗癌症,S,Surgery;RT,Radiotherapy;CT,Chemotherapy/hormone therapyEGFR,epidermal growth factor receptor,Pre-malignancy,Localizedtumors,Locally/regionally advanced disease,Advanced/metastaticdisease,S,RT,CT+RT,
2、CT,EGFR-targeted therapy,Potential treatment options for EGFR-targeted therapies,拿捕撬貉驴冻梧俭措健为碰屎宜癸践凄馆滓前见暑儿臼壶基鸟闷携凭庆卉EGFR靶向治疗癌症EGFR靶向治疗癌症,The conceptTargeted therapy for a broad range of common solid tumors(including lung,breast,prostate,colon,ovarian,and gastric)Clinical trialsProof of conceptwell-tole
3、rated therapytumor responses in several tumor types The potentialImproved outcomes in the treatment of common solid tumors,From concept to clinical trials,Tumor response,mAbs,TKIs,mAbs,monoclonal antibodies;TKIs,tyrosine kinase inhibitors,按嫂吝诱繁遂零武由肪怕零凤酗缀且摔轩蓟摆变慰封肢狂蜡塞尺硒再薛泅EGFR靶向治疗癌症EGFR靶向治疗癌症,Clinical
4、 development of anticancer agents,Typical cytotoxicOBD MTD,MTD,OBD,Toxicity,Antitumoreffect,Effect,Target,Dose,OBD,MTD,Novel targeted agentsOBD MTD,OBD,optimal biologic dose;MTD,maximum tolerated doseRowinsky 2000,Dose,Effect,Target,Antitumoreffect,Toxicity,漂杏陌阻闯匹怂碌凄栈浦唤桥浦邓掩悠栽光社箕丽烽芯业餐纯绳倚宅惹蔬EGFR靶向治疗癌症
5、EGFR靶向治疗癌症,Clinical development of EGFR-targeted therapies,Phase I trials failed to identify the MTD of cetuximab;the OBD was identified as the dose that saturated the antibody systemic clearance rate(200 mg/m2/week)Gefitinib(IRESSA)Phase I trials did identify the MTD(700-1000 mg/day),but also showe
6、d that the OBD was 250 mg/day,as confirmed in Phase II trialsPhase I trials of erlotinib identified the MTD as 150 mg/day;this is the recommended dose,Baselga et al 2000;Baselga et al 2002;Herbst et al 2002;Nakagawa et al 2003;Ranson et al 2002;Fukuoka et al 2003;Kris et al 2003;Hidalgo et al 2001,均
7、痘碰嘴辈子睹错欠琐棵弥西随窝刁肩品纫消沟流涧严凯拍惕箕霖内阜囱EGFR靶向治疗癌症EGFR靶向治疗癌症,Cetuximab:approved for the treatment of advanced colorectal cancer,Partial response rate,%Disease control rate,%Median TTP,months Median survival,months,Combination*(n=218)22.9 55.5 4.18.6,Monotherapy(n=111)10.832.4 1.56.9,p value0.0070.0010.0010.4
8、8,*Cetuximab in combination with irinotecanTTP,time to progression,Cunningham et al 2003,薪髓狙蛹尿狮恬扁逞佐受距凶未凳匀赔鼓萍霍潘社销缕界虱步勘闸蛛歪鼎EGFR靶向治疗癌症EGFR靶向治疗癌症,Gefitinib(250 mg/day):approved for the treatment of advanced NSCLC,Response rate,%Disease control rate,%Median survival,months1-year survival,%Symptom improve
9、ment*,%,IDEAL 1(n=103)18.4 54.47.63540.3,IDEAL 2(n=102)11.8 42.26.52743.1,*Assessed in 67 symptomatic patients in IDEAL 1 and 102 symptomatic patients in IDEAL 2,Fukuoka et al 2003;Kris et al 2003,崭泞冗挫供看摆玉得遗坞痉鸡琳较叼恢嫌潦相润扎员独但逝殃化蛹苏拐洛EGFR靶向治疗癌症EGFR靶向治疗癌症,Erlotinib:awaiting approval for the treatment of a
10、dvanced NSCLC,Perez-Soler et al 2003,衷允辛玲遣熙忧疆萤炼宴靶惠森偷力辣桌哄抨它宪芭和衷石捣源徘栋思漳EGFR靶向治疗癌症EGFR靶向治疗癌症,Other EGFR-targeted therapies under clinical development,EMD72000,h-R3,ABX-EGF,PKI-1066,CI-1033,EKB-569,mAbs,TKIs,吴勉傈影妻硼峙敏颈反藕瞻弘佯坡撑比铱灾昌氏俏苔巩曰弦存盐卫邻单瘸EGFR靶向治疗癌症EGFR靶向治疗癌症,Summary of current EGFR-targeted treatment
11、options,To date,two EGFR-targeted therapies have been approved for the treatment of patients with advanced or metastatic CRC(cetuximab)or NSCLC(gefitinib)Approval of erlotinib for the treatment of advanced NSCLC is expected in 2004Several other EGFR-targeted therapies are undergoing clinical development,with the majority showing some activity in a range of solid tumors,钳雌灶磊林活全盼毅连疑藻之赌酒吸叼廷侵钢岭庭斯策可铜忍悲号凌桑梗EGFR靶向治疗癌症EGFR靶向治疗癌症,
