恶性黑色素瘤课件

恶性黑色素瘤恶性黑色素瘤1概述好发于白色人种，我国的发病率并不高59，580的新发病例，7770死于该病(2005)发病率上升:男性上升最快,女性仅次于肺癌发病中位年龄:45-55岁概述好发于白色人种，我国的发病率并不高2发病因素紫外线照射先前存在的黑色素病变（如结构不良痣）遗传因素外伤内分泌化学致癌物质免疫缺陷发病因素紫外线照射3临床表现雀斑型占10-15%多见于60-70岁，女性较多好发于头、颈、手背等暴露部位为4型中恶性程度最低的一种较大的、平的棕黄色或棕色病灶表浅蔓延型最多见，约占70%好发于50岁左右,无性别差异女性多发于肢体，男性多发于躯干其恶性程度介于雀斑型和结节型之间略隆起的色素性损害，边界不规则，色素不均匀，呈混杂颜色临床表现雀斑型占10-15%4临床表现结节型占12%左右平均发病年龄50岁左右，男女比例为2:1好发于背部，垂直生长为其唯一生长方式4型中最恶性的一型灰色带有桃红色彩的结节，当病灶继续生长时其颜色变成蓝黑色，并较早发生溃疡和淋巴结转移肢端色斑样黑色素瘤主要发生于手掌、脚底及甲下有辐射生长期和垂直生长期两个过程辐射生长期的病灶镶嵌棕黄、棕褐或黑色，并不高出皮面辐射生长期持续1年左右，如不及时处理，病灶呈结节状隆起，提示进入垂直生长期，淋巴结转移率增加，预后差临床表现结节型占12%左右5镜下肿瘤浸润深度镜下肿瘤浸润深度6ClarkI:肿瘤局限于表皮的基底膜内(原位黑色素瘤)II:肿瘤已穿透基底膜,但仅浸润至真皮乳头层III:肿瘤沿真皮乳头层和网状层积聚IV:肿瘤已浸润真皮网状层V:肿瘤浸润至皮下组织

(带有主观性,如真皮乳头层和网状层无明确界限,III/IV缺乏衡量标准)ClarkI:肿瘤局限于表皮的基底膜内(原位黑色素瘤)7Breslow目镜测微器直接测量肿瘤厚度估计预后

≤0.75mm0.76~1.5mm1.51~4.00mm

＞4.00mm亦有其他分档Breslow目镜测微器直接测量肿瘤厚度8AJCCStagingAmericanJointCommitteeonCancerAJCCStagingAmericanJointCom9TNM分期该领域主要的进展AJCC的新的分期系统前哨淋巴结活检的应用I期至III期的局限性恶黑分期中主要的进展有Breslow肿瘤厚度和有否溃疡应用于T分期Clark分期仅应用于肿瘤厚度≤1.0mm的分期受累的淋巴结数目和是否临床可扪及应用于N分期卫星灶或肿瘤与淋巴结中途转移病灶包括于N分期TNM分期该领域主要的进展10恶性黑色素瘤课件11恶性黑色素瘤课件12恶性黑色素瘤课件13生存曲线BalchCM,etal.JClinOncol2001;19:3635生存曲线BalchCM,etal.JClinOn14预后因素原发病灶肿瘤厚度溃疡浸润水平淋巴侵犯淋巴结转移数目远处转移血LDH水平预后因素原发病灶15淋巴结阳性数目BalchCM,etal.JClinOncol2001;19:3622淋巴结阳性数目BalchCM,etal.JClin16转移部位BalchCM,etal.JClinOncol2001;19:3622转移部位BalchCM,etal.JClinOn17辅助治疗化疗无益处生物治疗和化疗联合等待SWOG0008(HD-IFN-α±CVD)免疫治疗辅助治疗化疗18辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α19辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α20PatientswithStageⅡB/ⅢMelanoma

(N=280)Observation(n=137)High-doseIFN-α(n=143)ECOG1684KirkwoodJM,etal.JClinOncol1996;14:71Regimen:20MU/m2IV5days/week×4weeks10MU/m2SCTIW×48weeksPatientswithObservationHigh-21疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol1996;14:71疗效RFS:Relapse-freesurvivalKi22毒性治疗延迟/中断:50%Ⅲ/Ⅳ度毒性:76%危及生命毒性:9%2例患者因肝功能衰竭死亡KirkwoodJM,etal.JClinOncol1996;14:71毒性治疗延迟/中断:50%KirkwoodJM,et23ECOG1690Observation(n=212)Low-doseIFN-α(n=215)High-doseIFN-α(n=215)PatientswithStageⅡB/ⅢMelanoma

(N=642)Regimen(Low-doseIFN-α):3MU/dSCTIW×2yearsKirkwoodJM,etal.JClinOncol2000;18:2444ECOG1690ObservationLow-doseI24疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2000;18:2444疗效RFS:Relapse-freesurvivalKi25毒性KirkwoodJM,etal.JClinOncol2000;18:2444毒性KirkwoodJM,etal.JClinO26PatientswithStageⅡB/ⅢMelanoma

(N=880)GMKvaccine(n=440)High-doseIFN-α(n=440)ECOG1694KirkwoodJM,etal.JClinOncol2001;19:2370Regimen:20MU/m2IV5days/week×4weeks10MU/m2SCTIW×48weeksPatientswithGMKvaccineHigh-27疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2001;19:2370疗效RFS:Relapse-freesurvivalKi28EORTC18952Observation(n=279)Intermediate-doseIFN-α(n=553)High-doseIFN-α(n=556)PatientswithStageⅡB/ⅢMelanoma

(N=1388)Regimen(IFN-α):10MU/m2IV5days/week×4weeks10MU/dSCTIW×1years

or5MU/dSCTIW×2yearsEggermont,AM,etal.Lancet2005;366:1189EORTC18952ObservationIntermed29疗效DMFI:distantmetastasisfreeintervalOS:OverallsurvivalEggermont,AM,etal.Lancet2005;366:1189疗效DMFI:distantmetastasisfre30毒性Eggermont,AM,etal.Lancet2005;366:1189毒性Eggermont,AM,etal.Lancet31比较RFS:Relapse-freesurvivalOS:Overallsurvival比较RFS:Relapse-freesurvival32辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α33PatientswithNode-positiveMelanoma

(N=444)Observation(n=219)Low-doseIFN-α(n=225)WHO16CascinelliN,etal.Lancet2001;358:866Regimen:3MU/m2SCTIW×3yearsCascinelliN,etal.Lancet1994;343:913PatientswithObservationLow-d34疗效RFS:Relapse-freesurvivalOS:OverallsurvivalCascinelliN,etal.Lancet1994;343:913CascinelliN,etal.Lancet2001;358:866疗效RFS:Relapse-freesurvivalCa35PatientswithStageⅡB/ⅢMelanoma

(N=674)Observation(n=336)Low-doseIFN-α(n=338)UKCCRHancockBW,etal.JClinOncol2004;22:53Regimen:3MU/m2SCTIW×2yearsPatientswithObservationLow-d36疗效RFS:Relapse-freesurvivalOS:OverallsurvivalHancockBW,etal.JClinOncol2004;22:53疗效RFS:Relapse-freesurvivalHa37辅助免疫治疗High-doseIFN-αLow-doseIFN-αIL-2TretinoinGM-CSFTumorvaccine辅助免疫治疗High-doseIFN-α38PatientswithT3/4N0M0Melanoma

(N=223)Observation(n=110)Low-doseIFN-α+IL-2(n=113)德国一项研究HauschildA,etal.JClinOncol2003;21:2883PatientswithObservationLow-d39方案(IFN-α+IL-2)IFN-α3MU/m2SCdays1-5week1IL-29MU/m2SCdays1-4week2IFN-α3MU/m2SCTIWweeks3-6Repeatedfor8cyclesHauschildA,etal.JClinOncol2003;21:2883方案(IFN-α+IL-2)IFN-α3MU/m2S40疗效RFS:Relapse-freesurvivalOS:OverallsurvivalHauschildA,etal.JClinOncol2003;21:2883疗效RFS:Relapse-freesurvivalHa41辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α42PatientswithStageⅡAⅡBMelanoma

(N=407)Low-doseIFN-α+Placebo(n=201)Low-doseIFN-α+Isotretinoin(n=206)德国研究Richtig

E,etal.JClinOncol2005;23:8655PatientswithLow-doseIFN-α+43方案(IFN-α+Isotrenoin)IFN-α3MU/m2SCTIW×2yearsIsotrenitoin20mg/30mgQD×2years(20mgforpts≤73kg,30mgforpts>73kg)

Richtig

E,etal.JClinOncol2005;23:8655方案(IFN-α+Isotrenoin)Richtig44疗效RFS:Relapse-freesurvivalOS:OverallsurvivalRichtig

E,etal.JClinOncol2005;23:8655疗效RFS:Relapse-freesurvivalRi45辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α46GM-CSF肿瘤疫苗

促树突细胞的增殖,

成熟和迁移诱导T细胞介导的免疫应答等待ECOG4697(GM-CSFvs观察)无生存益处购买不到等待与其他药物联合的研究GM-CSF肿瘤疫苗促树突细47转移后的治疗转移后的治疗48单药有效细胞毒药物单药有效细胞毒药物49常用方案单药DacarbazineTemozolomide联合化疗CDB(DDP+DTIC+BCNU)CDBT(DDP+DTIC+BCNU+TAM)CVD(DDP+VLB+DTIC)常用方案单药50TAM?TAM?51PatientswithAdvancedMelanoma

(N=184)DDP+DTIC+BCNU(n=92)DDP+DTIC+BCNU+TAM(n=92)NCIStudyCreaganET,etal.JClinOncol1999;17:1884PatientswithDDP+DTIC+BCN52方案CDB:DDP+DTIC+BCNUDDP25mg/m2days1-3DTIC220mg/m2days1-3BCNU150mg/m2day1everyotherdayDDP+DTIC+BCNU+TAMTAM20mgQDRepeatedevery3wksCreaganET,etal.JClinOncol1999;17:1884方案CDB:DDP+DTIC+BCNUCreaga53疗效ORR:overallresponserateTTP:timetoprogressionOS:overallsurvivalCreaganET,etal.JClinOncol1999;17:1884疗效ORR:overallresponserateCr54单药vs联合化疗单药vs联合化疗55PatientswithAdvancedMelanoma

(N=240)DTIC(n=121)DDP+DTIC+BCNU+TAM(n=119)研究设计ChapmanPB,etal.JClinOncol1999;17:2745PatientswithDTICDDP+DTIC+56方案DTICaloneDTIC1000mg/m2day1CDBT:DDP+DTIC+BCNU+TAMDDP25mg/m2days1-3DTIC220mg/m2days1-3BCNU150mg/m2day1everyothercycleTAM20mgQDRepeatedevery3wksChapmanPB,etal.JClinOncol1999;17:2745方案DTICaloneChapmanPB,etal.57疗效ORR:overallresponserateOS:overallresponseChapmanPB,etal.JClinOncol1999;17:2745疗效ORR:overallresponserateCh58毒性(Ⅲ/Ⅳ度)ChapmanPB,etal.JClinOncol1999;17:2745毒性(Ⅲ/Ⅳ度)ChapmanPB,etal.J59DTICvsTemozolomideDTICvsTemozolomide60PatientswithAdvancedMelanoma

(N=305)DTIC250mg/m2days1-5Q3wks(n=149)Temozolomide200mg/m2days1-5Q4wks(n=156)研究设计MiddletonMR,etal.JClinOncol2000;18:158PatientswithDTICTemozolomide61疗效ORR:overallresponseratePFS:progressionfreesurvivalOS:overallresponseMiddletonMR,etal.JClinOncol2000;18:158疗效ORR:overallresponserateMi62毒性和生活质量QOL:qualityoflifeMiddletonMR,etal.JClinOncol2000;18:158KiebertGM,etal.CancerInvest2003;21:821毒性和生活质量QOL:qualityoflifeMid63化疗vs化疗联合生物治疗化疗vs化疗联合生物治疗64PatientswithAdvancedMelanoma

(N=282)Temozolomide(n=139)Temozolomide+IFN-α(n=143)DeCOGStudyKaufmannR,etal.JClinOncol2005;23:9001PatientswithTemozolomideTemo65方案Temozolomide单药200mg/m2days1-5Q4wksTemozolomide+IFN-αTemozolomide:200mg/m2days1-5Q4wksIFN-α:5MU/m2TIWKaufmannR,etal.JClinOncol2005;23:9001方案Temozolomide单药KaufmannR,e66疗效ORR:overallresponseratePFS:progression-freesurvivalOS:overallresponseKaufmannR,etal.JClinOncol2005;23:9001疗效ORR:overallresponserateKa67毒性(Ⅲ/Ⅳ度)KaufmannR,etal.JClinOncol2005;23:9001毒性(Ⅲ/Ⅳ度)KaufmannR,etal.J68联合IFN+IL-2?联合IFN+IL-2?69PatientswithAdvancedMelanoma

(N=183)CVD(n=92)CVD+IFN-α+IL-2(n=91)MDACCStudyEtonO,etal.JClinOncol2002;20:2045PatientswithCVDCVD+IFN-α+70方案CVDDDP20mg/m2d1-4,22-25VLB2mg/m2d1-4,22-25DTIC800mg/m2d1,22Repeatedevery6wksCVD+IFN-α+IL-2DDP20mg/m2d1-4,22-25VLB1.5mg/m2d1-4,22-25DTIC800mg/m2d1,22IFN-α5MU/m2d5-9,17-21,26-30IL-29MU/m2d5-8,17-20,26-29Repeatedevery6wks方案CVDCVD+IFN-α+IL-271疗效ORR:overallresponserateTTP:timetoprogressionOS:overallresponseEtonO,etal.JClinOncol2002;20:2045疗效ORR:overallresponserateEt72血液学毒性EtonO,etal.JClinOncol2002;20:2045血液学毒性EtonO,etal.JClinOnc73非血液学毒性EtonO,etal.JClinOncol2002;20:2045非血液学毒性EtonO,etal.JClinOn74PatientswithAdvancedMelanoma

(N=405)CVD(n=201)CVD+IFN-α+IL-2(n=204)ECOG3695AtkinsMB,etal.ASCO2003;22:2847aPatientswithCVDCVD+IFN-α+75方案CVDDDP20mg/m2d1-4VLB1.2mg/m2d1-4DTIC800mg/m2d1Repeatedevery3wksCVD+IFN-α+IL-2DDP20mg/m2d1-4VLB1.2mg/m2d1-4DTIC800mg/m2d1IFN-α5MU/m2d1-5,8,10,12IL-29MU/m2CIV96hoursRepeatedevery3wksAtkinsMB,etal.ASCO2003;22:2847a方案CVDCVD+IFN-α+IL-2AtkinsM76疗效ORR:overallresponseratePFS:progression-freesurvivalOS:overallresponseAtkinsMB,etal.ASCO2003;22:2847a疗效ORR:overallresponserateAt77PatientswithAdvancedMelanoma

(N=144)CVD(n=72)CVD+IFN-α+IL-2(n=72)意大利研究BajettaE,etal.AnnOncol2006;17:571PatientswithCVDCVD+IFN-α+78方案CVDDDP30mg/m2d1-3VDS2.5mg/m2d1DTIC250mg/m2d1-3

Repeatedevery3wksCVD+IFN-α+IL-2DDP30mg/m2d1-3VDS2.5mg/m2d1DTIC250mg/m2d1-3IFN-α5MU/m2d1-5IL-29MUd1-5,8-15Repeatedevery3wksBajettaE,etal.AnnOncol2006;17:571方案CVDCVD+IFN-α+IL-2Bajetta79疗效ORR:overallresponserateTTP:timetoprogressionOS:overallresponseBajettaE,etal.AnnOncol2006;17:571疗效ORR:overallresponserateBa80毒性(Ⅲ/Ⅳ度)BajettaE,etal.AnnOncol2006;17:571毒性(Ⅲ/Ⅳ度)BajettaE,etal.Ann81解救化疗解救化疗82Paclitaxel+CBP31例转移性恶性黑色素瘤94%先前DTIC/TMZ治疗失败方案:Paclitaxel100mg/m2days1,8,15CBPAUC2days1,8,15

每4周重复RaoRD,etal.Cancer2006;106:375Paclitaxel+CBP31例转移性恶性黑色素瘤R83疗效ORR:overallresponserateSD:stablediseasePFS:progression-freesurvivalOS:overallresponseRaoRD,etal.Cancer2006;106:375疗效ORR:overallresponserateRa84靶向治疗靶向治疗85SorafenibRaf激酶小分子抑制剂80%的恶性黑色素瘤存在B-raf突变单药治疗结果令人失望剂量:400mgBIDpoSorafenibRaf激酶小分子抑制剂86联合药物治疗AmaravadiRK,etal.ASCO2006;24:8900aLoriganP,etal.ASCO2006;24:8012aFlahertyKT,etal.ASCO2004;22:7507a联合药物治疗AmaravadiRK,etal.AS87

THANKS!THANKS!88此课件下载可自行编辑修改，供参考！部分内容来源于网络，如有侵权请与我联系删除！此课件下载可自行编辑修改，供参考！89恶性黑色素瘤恶性黑色素瘤90概述好发于白色人种，我国的发病率并不高59，580的新发病例，7770死于该病(2005)发病率上升:男性上升最快,女性仅次于肺癌发病中位年龄:45-55岁概述好发于白色人种，我国的发病率并不高91发病因素紫外线照射先前存在的黑色素病变（如结构不良痣）遗传因素外伤内分泌化学致癌物质免疫缺陷发病因素紫外线照射92临床表现雀斑型占10-15%多见于60-70岁，女性较多好发于头、颈、手背等暴露部位为4型中恶性程度最低的一种较大的、平的棕黄色或棕色病灶表浅蔓延型最多见，约占70%好发于50岁左右,无性别差异女性多发于肢体，男性多发于躯干其恶性程度介于雀斑型和结节型之间略隆起的色素性损害，边界不规则，色素不均匀，呈混杂颜色临床表现雀斑型占10-15%93临床表现结节型占12%左右平均发病年龄50岁左右，男女比例为2:1好发于背部，垂直生长为其唯一生长方式4型中最恶性的一型灰色带有桃红色彩的结节，当病灶继续生长时其颜色变成蓝黑色，并较早发生溃疡和淋巴结转移肢端色斑样黑色素瘤主要发生于手掌、脚底及甲下有辐射生长期和垂直生长期两个过程辐射生长期的病灶镶嵌棕黄、棕褐或黑色，并不高出皮面辐射生长期持续1年左右，如不及时处理，病灶呈结节状隆起，提示进入垂直生长期，淋巴结转移率增加，预后差临床表现结节型占12%左右94镜下肿瘤浸润深度镜下肿瘤浸润深度95ClarkI:肿瘤局限于表皮的基底膜内(原位黑色素瘤)II:肿瘤已穿透基底膜,但仅浸润至真皮乳头层III:肿瘤沿真皮乳头层和网状层积聚IV:肿瘤已浸润真皮网状层V:肿瘤浸润至皮下组织

(带有主观性,如真皮乳头层和网状层无明确界限,III/IV缺乏衡量标准)ClarkI:肿瘤局限于表皮的基底膜内(原位黑色素瘤)96Breslow目镜测微器直接测量肿瘤厚度估计预后

≤0.75mm0.76~1.5mm1.51~4.00mm

＞4.00mm亦有其他分档Breslow目镜测微器直接测量肿瘤厚度97AJCCStagingAmericanJointCommitteeonCancerAJCCStagingAmericanJointCom98TNM分期该领域主要的进展AJCC的新的分期系统前哨淋巴结活检的应用I期至III期的局限性恶黑分期中主要的进展有Breslow肿瘤厚度和有否溃疡应用于T分期Clark分期仅应用于肿瘤厚度≤1.0mm的分期受累的淋巴结数目和是否临床可扪及应用于N分期卫星灶或肿瘤与淋巴结中途转移病灶包括于N分期TNM分期该领域主要的进展99恶性黑色素瘤课件100恶性黑色素瘤课件101恶性黑色素瘤课件102生存曲线BalchCM,etal.JClinOncol2001;19:3635生存曲线BalchCM,etal.JClinOn103预后因素原发病灶肿瘤厚度溃疡浸润水平淋巴侵犯淋巴结转移数目远处转移血LDH水平预后因素原发病灶104淋巴结阳性数目BalchCM,etal.JClinOncol2001;19:3622淋巴结阳性数目BalchCM,etal.JClin105转移部位BalchCM,etal.JClinOncol2001;19:3622转移部位BalchCM,etal.JClinOn106辅助治疗化疗无益处生物治疗和化疗联合等待SWOG0008(HD-IFN-α±CVD)免疫治疗辅助治疗化疗107辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α108辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α109PatientswithStageⅡB/ⅢMelanoma

(N=280)Observation(n=137)High-doseIFN-α(n=143)ECOG1684KirkwoodJM,etal.JClinOncol1996;14:71Regimen:20MU/m2IV5days/week×4weeks10MU/m2SCTIW×48weeksPatientswithObservationHigh-110疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol1996;14:71疗效RFS:Relapse-freesurvivalKi111毒性治疗延迟/中断:50%Ⅲ/Ⅳ度毒性:76%危及生命毒性:9%2例患者因肝功能衰竭死亡KirkwoodJM,etal.JClinOncol1996;14:71毒性治疗延迟/中断:50%KirkwoodJM,et112ECOG1690Observation(n=212)Low-doseIFN-α(n=215)High-doseIFN-α(n=215)PatientswithStageⅡB/ⅢMelanoma

(N=642)Regimen(Low-doseIFN-α):3MU/dSCTIW×2yearsKirkwoodJM,etal.JClinOncol2000;18:2444ECOG1690ObservationLow-doseI113疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2000;18:2444疗效RFS:Relapse-freesurvivalKi114毒性KirkwoodJM,etal.JClinOncol2000;18:2444毒性KirkwoodJM,etal.JClinO115PatientswithStageⅡB/ⅢMelanoma

(N=880)GMKvaccine(n=440)High-doseIFN-α(n=440)ECOG1694KirkwoodJM,etal.JClinOncol2001;19:2370Regimen:20MU/m2IV5days/week×4weeks10MU/m2SCTIW×48weeksPatientswithGMKvaccineHigh-116疗效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2001;19:2370疗效RFS:Relapse-freesurvivalKi117EORTC18952Observation(n=279)Intermediate-doseIFN-α(n=553)High-doseIFN-α(n=556)PatientswithStageⅡB/ⅢMelanoma

(N=1388)Regimen(IFN-α):10MU/m2IV5days/week×4weeks10MU/dSCTIW×1years

or5MU/dSCTIW×2yearsEggermont,AM,etal.Lancet2005;366:1189EORTC18952ObservationIntermed118疗效DMFI:distantmetastasisfreeintervalOS:OverallsurvivalEggermont,AM,etal.Lancet2005;366:1189疗效DMFI:distantmetastasisfre119毒性Eggermont,AM,etal.Lancet2005;366:1189毒性Eggermont,AM,etal.Lancet120比较RFS:Relapse-freesurvivalOS:Overallsurvival比较RFS:Relapse-freesurvival121辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α122PatientswithNode-positiveMelanoma

(N=444)Observation(n=219)Low-doseIFN-α(n=225)WHO16CascinelliN,etal.Lancet2001;358:866Regimen:3MU/m2SCTIW×3yearsCascinelliN,etal.Lancet1994;343:913PatientswithObservationLow-d123疗效RFS:Relapse-freesurvivalOS:OverallsurvivalCascinelliN,etal.Lancet1994;343:913CascinelliN,etal.Lancet2001;358:866疗效RFS:Relapse-freesurvivalCa124PatientswithStageⅡB/ⅢMelanoma

(N=674)Observation(n=336)Low-doseIFN-α(n=338)UKCCRHancockBW,etal.JClinOncol2004;22:53Regimen:3MU/m2SCTIW×2yearsPatientswithObservationLow-d125疗效RFS:Relapse-freesurvivalOS:OverallsurvivalHancockBW,etal.JClinOncol2004;22:53疗效RFS:Relapse-freesurvivalHa126辅助免疫治疗High-doseIFN-αLow-doseIFN-αIL-2TretinoinGM-CSFTumorvaccine辅助免疫治疗High-doseIFN-α127PatientswithT3/4N0M0Melanoma

(N=223)Observation(n=110)Low-doseIFN-α+IL-2(n=113)德国一项研究HauschildA,etal.JClinOncol2003;21:2883PatientswithObservationLow-d128方案(IFN-α+IL-2)IFN-α3MU/m2SCdays1-5week1IL-29MU/m2SCdays1-4week2IFN-α3MU/m2SCTIWweeks3-6Repeatedfor8cyclesHauschildA,etal.JClinOncol2003;21:2883方案(IFN-α+IL-2)IFN-α3MU/m2S129疗效RFS:Relapse-freesurvivalOS:OverallsurvivalHauschildA,etal.JClinOncol2003;21:2883疗效RFS:Relapse-freesurvivalHa130辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α131PatientswithStageⅡAⅡBMelanoma

(N=407)Low-doseIFN-α+Placebo(n=201)Low-doseIFN-α+Isotretinoin(n=206)德国研究Richtig

E,etal.JClinOncol2005;23:8655PatientswithLow-doseIFN-α+132方案(IFN-α+Isotrenoin)IFN-α3MU/m2SCTIW×2yearsIsotrenitoin20mg/30mgQD×2years(20mgforpts≤73kg,30mgforpts>73kg)

Richtig

E,etal.JClinOncol2005;23:8655方案(IFN-α+Isotrenoin)Richtig133疗效RFS:Relapse-freesurvivalOS:OverallsurvivalRichtig

E,etal.JClinOncol2005;23:8655疗效RFS:Relapse-freesurvivalRi134辅助免疫治疗高剂量IFN-α低剂量IFN-αIL-2TretinoinGM-CSF肿瘤疫苗辅助免疫治疗高剂量IFN-α135GM-CSF肿瘤疫苗

促树突细胞的增殖,

成熟和迁移诱导T细胞介导的免疫应答等待ECOG4697(GM-CSFvs观察)无生存益处购买不到等待与其他药物联合的研究GM-CSF肿瘤疫苗促树突细136转移后的治疗转移后的治疗137单药有效细胞毒药物单药有效细胞毒药物138常用方案单药DacarbazineTemozolomide联合化疗CDB(DDP+DTIC+BCNU)CDBT(DDP+DTIC+BCNU+TAM)CVD(DDP+VLB+DTIC)常用方案单药139TAM?TAM?140PatientswithAdvancedMelanoma

(N=184)DDP+DTIC+BCNU(n=92)DDP+DTIC+BCNU+TAM(n=92)NCIStudyCreaganET,etal.JClinOncol1999;17:1884PatientswithDDP+DTIC+BCN141方案CDB:DDP+DTIC+BCNUDDP25mg/m2days1-3DTIC220mg/m2days1-3BCNU150mg/m2day1everyotherdayDDP+DTIC+BCNU+TAMTAM20mgQDRepeatedevery3wksCreaganET,etal.JClinOncol1999;17:1884方案CDB:DDP+DTIC+BCNUCreaga142疗效ORR:overallresponserateTTP:timetoprogressionOS:overallsurvivalCreaganET,etal.JClinOncol1999;17:1884疗效ORR:overallresponserateCr143单药vs联合化疗单药vs联合化疗144PatientswithAdvancedMelanoma

(N=240)DTIC(n=121)DDP+DTIC+BCNU+TAM(n=119)研究设计ChapmanPB,etal.JClinOncol1999;17:2745PatientswithDTICDDP+DTIC+145方案DTICaloneDTIC1000mg/m2day1CDBT:DDP+DTIC+BCNU+TAMDDP25mg/m2days1-3DTIC220mg/m2days1-3BCNU150mg/m2day1everyothercycleTAM20mgQDRepeatedevery3wksChapmanPB,etal.JClinOncol1999;17:2745方案DTICaloneChapmanPB,etal.146疗效ORR:overallresponserateOS:overallresponseChapmanPB,etal.JClinOncol1999;17:2745疗效ORR:overallresponserateCh147毒性(Ⅲ/Ⅳ度)ChapmanPB,etal.JClinOncol1999;17:2745毒性(Ⅲ/Ⅳ度)ChapmanPB,etal.J148DTICvsTemozolomideDTICvsTemozolomide149PatientswithAdvancedMelanoma

(N=305)DTIC250mg/m2days1-5Q3wks(n=149)Temozolomide200mg/m2days1-5Q4wks(n=156)研究设计MiddletonMR,etal.JClinOncol2000;18:158PatientswithDTICTemozolomide150疗效ORR:overallresponseratePFS:progressionfreesurvivalOS:overallresponseMiddletonMR,etal.JClinOncol2000;18:158疗效ORR:overallresponserateMi151毒性和生活质量QOL:qualityoflifeMiddletonMR,etal.JClinOncol2000;18:158KiebertGM,etal.CancerInvest2003;21:821毒性和生活质量QOL:qualityoflifeMid152化疗vs化疗联合生物治疗化疗vs化疗联合生物治疗153PatientswithAdvancedMelanoma

(N=282)Temozolomide(n=139)Temozolomide+IFN-α(n=143)DeCOGStudyKaufmannR,etal.JClinOncol2005;23:9001PatientswithTemozolomideTemo154方案Temozolomide单药200mg/m2days1-5Q4wksTemozolomide+IFN-αTemozolomide:200mg/m2days1-5Q4wksIFN-α:5MU/m2TIWKaufmannR,etal.JClinOncol2005;23:9001方案Temozolomide单药KaufmannR,e155疗效ORR:overallresponseratePFS:progression-freesurvivalOS:overallresponseKaufmannR,etal.JClinOncol2005;23:9001疗效ORR:overallresponserateKa156毒性(Ⅲ/Ⅳ度)KaufmannR,etal.JClinOncol2005;23:9001毒性(Ⅲ/Ⅳ度)KaufmannR,etal.J157联合IFN+IL-2?联合IFN+IL-2?158PatientswithAdvancedMelanoma

(N=183)CVD(n=92)CVD+IFN-α+IL-2(n=91)MDACCStudyEtonO,etal.JClinOncol2002;20:2045PatientswithCVDCVD+IFN-α+159方案CVDDDP20mg/m2d1-4,22-25VLB2mg/m2d1-4,22-25DTIC800mg/m2d1,22Repeatedevery6wksCVD+IFN-α+IL-2DDP20mg/m2d1-4,22-25VLB1.5mg/m2d1-4,22-25DTIC800mg/m2d1,22IFN-α5MU/m2d5-9,17-21,26-30IL-29MU/m2d5-8,17-20,26-29Repeatedevery6wks方案CVDCVD+IFN-α+IL-2160疗效ORR:overallresponserateTTP:timetoprogressionO