惡性黑色素瘤課件

惡性黑色素瘤惡性黑色素瘤1概述好發(fā)于白色人種，我國的發(fā)病率并不高59，580的新發(fā)病例，7770死于該病(2005)發(fā)病率上升:男性上升最快,女性僅次于肺癌發(fā)病中位年齡:45-55歲概述好發(fā)于白色人種，我國的發(fā)病率并不高2發(fā)病因素紫外線照射先前存在的黑色素病變（如結(jié)構(gòu)不良痣）遺傳因素外傷內(nèi)分泌化學致癌物質(zhì)免疫缺陷發(fā)病因素紫外線照射3臨床表現(xiàn)雀斑型占10-15%多見于60-70歲，女性較多好發(fā)于頭、頸、手背等暴露部位為4型中惡性程度最低的一種較大的、平的棕黃色或棕色病灶表淺蔓延型最多見，約占70%好發(fā)于50歲左右,無性別差異女性多發(fā)于肢體，男性多發(fā)于軀干其惡性程度介于雀斑型和結(jié)節(jié)型之間略隆起的色素性損害，邊界不規(guī)則，色素不均勻，呈混雜顏色臨床表現(xiàn)雀斑型占10-15%4臨床表現(xiàn)結(jié)節(jié)型占12%左右平均發(fā)病年齡50歲左右，男女比例為2:1好發(fā)于背部，垂直生長為其唯一生長方式4型中最惡性的一型灰色帶有桃紅色彩的結(jié)節(jié)，當病灶繼續(xù)生長時其顏色變成藍黑色，并較早發(fā)生潰瘍和淋巴結(jié)轉(zhuǎn)移肢端色斑樣黑色素瘤主要發(fā)生于手掌、腳底及甲下有輻射生長期和垂直生長期兩個過程輻射生長期的病灶鑲嵌棕黃、棕褐或黑色，并不高出皮面輻射生長期持續(xù)1年左右，如不及時處理，病灶呈結(jié)節(jié)狀隆起，提示進入垂直生長期，淋巴結(jié)轉(zhuǎn)移率增加，預后差臨床表現(xiàn)結(jié)節(jié)型占12%左右5鏡下腫瘤浸潤深度鏡下腫瘤浸潤深度6ClarkI:腫瘤局限于表皮的基底膜內(nèi)(原位黑色素瘤)II:腫瘤已穿透基底膜,但僅浸潤至真皮乳頭層III:腫瘤沿真皮乳頭層和網(wǎng)狀層積聚IV:腫瘤已浸潤真皮網(wǎng)狀層V:腫瘤浸潤至皮下組織

(帶有主觀性,如真皮乳頭層和網(wǎng)狀層無明確界限,III/IV缺乏衡量標準)ClarkI:腫瘤局限于表皮的基底膜內(nèi)(原位黑色素瘤)7Breslow目鏡測微器直接測量腫瘤厚度估計預后

≤0.75mm0.76~1.5mm1.51~4.00mm

＞4.00mm亦有其他分檔Breslow目鏡測微器直接測量腫瘤厚度8AJCCStagingAmericanJointCommitteeonCancerAJCCStagingAmericanJointCom9TNM分期該領(lǐng)域主要的進展AJCC的新的分期系統(tǒng)前哨淋巴結(jié)活檢的應用I期至III期的局限性惡黑分期中主要的進展有Breslow腫瘤厚度和有否潰瘍應用于T分期Clark分期僅應用于腫瘤厚度≤1.0mm的分期受累的淋巴結(jié)數(shù)目和是否臨床可捫及應用于N分期衛(wèi)星灶或腫瘤與淋巴結(jié)中途轉(zhuǎn)移病灶包括于N分期TNM分期該領(lǐng)域主要的進展10惡性黑色素瘤課件11惡性黑色素瘤課件12惡性黑色素瘤課件13生存曲線BalchCM,etal.JClinOncol2001;19:3635生存曲線BalchCM,etal.JClinOn14預后因素原發(fā)病灶腫瘤厚度潰瘍浸潤水平淋巴侵犯淋巴結(jié)轉(zhuǎn)移數(shù)目遠處轉(zhuǎn)移血LDH水平預后因素原發(fā)病灶15淋巴結(jié)陽性數(shù)目BalchCM,etal.JClinOncol2001;19:3622淋巴結(jié)陽性數(shù)目BalchCM,etal.JClin16轉(zhuǎn)移部位BalchCM,etal.JClinOncol2001;19:3622轉(zhuǎn)移部位BalchCM,etal.JClinOn17輔助治療化療無益處生物治療和化療聯(lián)合等待SWOG0008(HD-IFN-α±CVD)免疫治療輔助治療化療18輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α19輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol1996;14:71療效RFS:Relapse-freesurvivalKi22毒性治療延遲/中斷: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毒性治療延遲/中斷: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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2000;18:2444療效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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2001;19:2370療效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療效DMFI:distantmetastasisfreeintervalOS:OverallsurvivalEggermont,AM,etal.Lancet2005;366:1189療效DMFI:distantmetastasisfre30毒性Eggermont,AM,etal.Lancet2005;366:1189毒性Eggermont,AM,etal.Lancet31比較RFS:Relapse-freesurvivalOS:Overallsurvival比較RFS:Relapse-freesurvival32輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量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療效RFS:Relapse-freesurvivalOS:OverallsurvivalCascinelliN,etal.Lancet1994;343:913CascinelliN,etal.Lancet2001;358:866療效RFS:Relapse-freesurvivalCa35PatientswithStageⅡB/ⅢMelanoma

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

(N=223)Observation(n=110)Low-doseIFN-α+IL-2(n=113)德國一項研究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療效RFS:Relapse-freesurvivalOS:OverallsurvivalHauschildA,etal.JClinOncol2003;21:2883療效RFS:Relapse-freesurvivalHa41輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α42PatientswithStageⅡAⅡBMelanoma

(N=407)Low-doseIFN-α+Placebo(n=201)Low-doseIFN-α+Isotretinoin(n=206)德國研究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療效RFS:Relapse-freesurvivalOS:OverallsurvivalRichtig

E,etal.JClinOncol2005;23:8655療效RFS:Relapse-freesurvivalRi45輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α46GM-CSF腫瘤疫苗

促樹突細胞的增殖,

成熟和遷移誘導T細胞介導的免疫應答等待ECOG4697(GM-CSFvs觀察)無生存益處購買不到等待與其他藥物聯(lián)合的研究GM-CSF腫瘤疫苗促樹突細47轉(zhuǎn)移后的治療轉(zhuǎn)移后的治療48單藥有效細胞毒藥物單藥有效細胞毒藥物49常用方案單藥DacarbazineTemozolomide聯(lián)合化療CDB(DDP+DTIC+BCNU)CDBT(DDP+DTIC+BCNU+TAM)CVD(DDP+VLB+DTIC)常用方案單藥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療效ORR:overallresponserateTTP:timetoprogressionOS:overallsurvivalCreaganET,etal.JClinOncol1999;17:1884療效ORR:overallresponserateCr54單藥vs聯(lián)合化療單藥vs聯(lián)合化療55PatientswithAdvancedMelanoma

(N=240)DTIC(n=121)DDP+DTIC+BCNU+TAM(n=119)研究設計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療效ORR:overallresponserateOS:overallresponseChapmanPB,etal.JClinOncol1999;17:2745療效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)研究設計MiddletonMR,etal.JClinOncol2000;18:158PatientswithDTICTemozolomide61療效ORR:overallresponseratePFS:progressionfreesurvivalOS:overallresponseMiddletonMR,etal.JClinOncol2000;18:158療效ORR:overallresponserateMi62毒性和生活質(zhì)量QOL:qualityoflifeMiddletonMR,etal.JClinOncol2000;18:158KiebertGM,etal.CancerInvest2003;21:821毒性和生活質(zhì)量QOL:qualityoflifeMid63化療vs化療聯(lián)合生物治療化療vs化療聯(lián)合生物治療64PatientswithAdvancedMelanoma

(N=282)Temozolomide(n=139)Temozolomide+IFN-α(n=143)DeCOGStudyKaufmannR,etal.JClinOncol2005;23:9001PatientswithTemozolomideTemo65方案Temozolomide單藥200mg/m2days1-5Q4wksTemozolomide+IFN-αTemozolomide:200mg/m2days1-5Q4wksIFN-α:5MU/m2TIWKaufmannR,etal.JClinOncol2005;23:9001方案Temozolomide單藥KaufmannR,e66療效ORR:overallresponseratePFS:progression-freesurvivalOS:overallresponseKaufmannR,etal.JClinOncol2005;23:9001療效ORR:overallresponserateKa67毒性(Ⅲ/Ⅳ度)KaufmannR,etal.JClinOncol2005;23:9001毒性(Ⅲ/Ⅳ度)KaufmannR,etal.J68聯(lián)合IFN+IL-2?聯(lián)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療效ORR:overallresponserateTTP:timetoprogressionOS:overallresponseEtonO,etal.JClinOncol2002;20:2045療效ORR:overallresponserateEt72血液學毒性EtonO,etal.JClinOncol2002;20:2045血液學毒性EtonO,etal.JClinOnc73非血液學毒性EtonO,etal.JClinOncol2002;20:2045非血液學毒性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療效ORR:overallresponseratePFS:progression-freesurvivalOS:overallresponseAtkinsMB,etal.ASCO2003;22:2847a療效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療效ORR:overallresponserateTTP:timetoprogressionOS:overallresponseBajettaE,etal.AnnOncol2006;17:571療效ORR:overallresponserateBa80毒性(Ⅲ/Ⅳ度)BajettaE,etal.AnnOncol2006;17:571毒性(Ⅲ/Ⅳ度)BajettaE,etal.Ann81解救化療解救化療82Paclitaxel+CBP31例轉(zhuǎn)移性惡性黑色素瘤94%先前DTIC/TMZ治療失敗方案:Paclitaxel100mg/m2days1,8,15CBPAUC2days1,8,15

每4周重復RaoRD,etal.Cancer2006;106:375Paclitaxel+CBP31例轉(zhuǎn)移性惡性黑色素瘤R83療效ORR:overallresponserateSD:stablediseasePFS:progression-freesurvivalOS:overallresponseRaoRD,etal.Cancer2006;106:375療效ORR:overallresponserateRa84靶向治療靶向治療85SorafenibRaf激酶小分子抑制劑80%的惡性黑色素瘤存在B-raf突變單藥治療結(jié)果令人失望劑量:400mgBIDpoSorafenibRaf激酶小分子抑制劑86聯(lián)合藥物治療AmaravadiRK,etal.ASCO2006;24:8900aLoriganP,etal.ASCO2006;24:8012aFlahertyKT,etal.ASCO2004;22:7507a聯(lián)合藥物治療AmaravadiRK,etal.AS87

THANKS!THANKS!88此課件下載可自行編輯修改，供參考！部分內(nèi)容來源于網(wǎng)絡，如有侵權(quán)請與我聯(lián)系刪除！此課件下載可自行編輯修改，供參考！89惡性黑色素瘤惡性黑色素瘤90概述好發(fā)于白色人種，我國的發(fā)病率并不高59，580的新發(fā)病例，7770死于該病(2005)發(fā)病率上升:男性上升最快,女性僅次于肺癌發(fā)病中位年齡:45-55歲概述好發(fā)于白色人種，我國的發(fā)病率并不高91發(fā)病因素紫外線照射先前存在的黑色素病變（如結(jié)構(gòu)不良痣）遺傳因素外傷內(nèi)分泌化學致癌物質(zhì)免疫缺陷發(fā)病因素紫外線照射92臨床表現(xiàn)雀斑型占10-15%多見于60-70歲，女性較多好發(fā)于頭、頸、手背等暴露部位為4型中惡性程度最低的一種較大的、平的棕黃色或棕色病灶表淺蔓延型最多見，約占70%好發(fā)于50歲左右,無性別差異女性多發(fā)于肢體，男性多發(fā)于軀干其惡性程度介于雀斑型和結(jié)節(jié)型之間略隆起的色素性損害，邊界不規(guī)則，色素不均勻，呈混雜顏色臨床表現(xiàn)雀斑型占10-15%93臨床表現(xiàn)結(jié)節(jié)型占12%左右平均發(fā)病年齡50歲左右，男女比例為2:1好發(fā)于背部，垂直生長為其唯一生長方式4型中最惡性的一型灰色帶有桃紅色彩的結(jié)節(jié)，當病灶繼續(xù)生長時其顏色變成藍黑色，并較早發(fā)生潰瘍和淋巴結(jié)轉(zhuǎn)移肢端色斑樣黑色素瘤主要發(fā)生于手掌、腳底及甲下有輻射生長期和垂直生長期兩個過程輻射生長期的病灶鑲嵌棕黃、棕褐或黑色，并不高出皮面輻射生長期持續(xù)1年左右，如不及時處理，病灶呈結(jié)節(jié)狀隆起，提示進入垂直生長期，淋巴結(jié)轉(zhuǎn)移率增加，預后差臨床表現(xiàn)結(jié)節(jié)型占12%左右94鏡下腫瘤浸潤深度鏡下腫瘤浸潤深度95ClarkI:腫瘤局限于表皮的基底膜內(nèi)(原位黑色素瘤)II:腫瘤已穿透基底膜,但僅浸潤至真皮乳頭層III:腫瘤沿真皮乳頭層和網(wǎng)狀層積聚IV:腫瘤已浸潤真皮網(wǎng)狀層V:腫瘤浸潤至皮下組織

(帶有主觀性,如真皮乳頭層和網(wǎng)狀層無明確界限,III/IV缺乏衡量標準)ClarkI:腫瘤局限于表皮的基底膜內(nèi)(原位黑色素瘤)96Breslow目鏡測微器直接測量腫瘤厚度估計預后

≤0.75mm0.76~1.5mm1.51~4.00mm

＞4.00mm亦有其他分檔Breslow目鏡測微器直接測量腫瘤厚度97AJCCStagingAmericanJointCommitteeonCancerAJCCStagingAmericanJointCom98TNM分期該領(lǐng)域主要的進展AJCC的新的分期系統(tǒng)前哨淋巴結(jié)活檢的應用I期至III期的局限性惡黑分期中主要的進展有Breslow腫瘤厚度和有否潰瘍應用于T分期Clark分期僅應用于腫瘤厚度≤1.0mm的分期受累的淋巴結(jié)數(shù)目和是否臨床可捫及應用于N分期衛(wèi)星灶或腫瘤與淋巴結(jié)中途轉(zhuǎn)移病灶包括于N分期TNM分期該領(lǐng)域主要的進展99惡性黑色素瘤課件100惡性黑色素瘤課件101惡性黑色素瘤課件102生存曲線BalchCM,etal.JClinOncol2001;19:3635生存曲線BalchCM,etal.JClinOn103預后因素原發(fā)病灶腫瘤厚度潰瘍浸潤水平淋巴侵犯淋巴結(jié)轉(zhuǎn)移數(shù)目遠處轉(zhuǎn)移血LDH水平預后因素原發(fā)病灶104淋巴結(jié)陽性數(shù)目BalchCM,etal.JClinOncol2001;19:3622淋巴結(jié)陽性數(shù)目BalchCM,etal.JClin105轉(zhuǎn)移部位BalchCM,etal.JClinOncol2001;19:3622轉(zhuǎn)移部位BalchCM,etal.JClinOn106輔助治療化療無益處生物治療和化療聯(lián)合等待SWOG0008(HD-IFN-α±CVD)免疫治療輔助治療化療107輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α108輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol1996;14:71療效RFS:Relapse-freesurvivalKi111毒性治療延遲/中斷: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毒性治療延遲/中斷: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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2000;18:2444療效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療效RFS:Relapse-freesurvivalOS:OverallsurvivalKirkwoodJM,etal.JClinOncol2001;19:2370療效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療效DMFI:distantmetastasisfreeintervalOS:OverallsurvivalEggermont,AM,etal.Lancet2005;366:1189療效DMFI:distantmetastasisfre119毒性Eggermont,AM,etal.Lancet2005;366:1189毒性Eggermont,AM,etal.Lancet120比較RFS:Relapse-freesurvivalOS:Overallsurvival比較RFS:Relapse-freesurvival121輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量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療效RFS:Relapse-freesurvivalOS:OverallsurvivalCascinelliN,etal.Lancet1994;343:913CascinelliN,etal.Lancet2001;358:866療效RFS:Relapse-freesurvivalCa124PatientswithStageⅡB/ⅢMelanoma

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

(N=223)Observation(n=110)Low-doseIFN-α+IL-2(n=113)德國一項研究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療效RFS:Relapse-freesurvivalOS:OverallsurvivalHauschildA,etal.JClinOncol2003;21:2883療效RFS:Relapse-freesurvivalHa130輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α131PatientswithStageⅡAⅡBMelanoma

(N=407)Low-doseIFN-α+Placebo(n=201)Low-doseIFN-α+Isotretinoin(n=206)德國研究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療效RFS:Relapse-freesurvivalOS:OverallsurvivalRichtig

E,etal.JClinOncol2005;23:8655療效RFS:Relapse-freesurvivalRi134輔助免疫治療高劑量IFN-α低劑量IFN-αIL-2TretinoinGM-CSF腫瘤疫苗輔助免疫治療高劑量IFN-α135GM-CSF腫瘤疫苗

促樹突細胞的增殖,

成熟和遷移誘導T細胞介導的免疫應答等待ECOG4697(GM-CSFvs觀察)無生存益處購買不到等待與其他藥物聯(lián)合的研究GM-CSF腫瘤疫苗促樹突細136轉(zhuǎn)移后的治療轉(zhuǎn)移后的治療137單藥有效細胞毒藥物單藥有效細胞毒藥物138常用方案單藥DacarbazineTemozolomide聯(lián)合化療CDB(DDP+DTIC+BCNU)CDBT(DDP+DTIC+BCNU+TAM)CVD(DDP+VLB+DTIC)常用方案單藥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療效ORR:overallresponserateTTP:timetoprogressionOS:overallsurvivalCreaganET,etal.JClinOncol1999;17:1884療效ORR:overallresponserateCr143單藥vs聯(lián)合化療單藥vs聯(lián)合化療144PatientswithAdvancedMelanoma

(N=240)DTIC(n=121)DDP+DTIC+BCNU+TAM(n=119)研究設計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療效ORR:overallresponserateOS:overallresponseChapmanPB,etal.JClinOncol1999;17:2745療效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)研究設計MiddletonMR,etal.JClinOncol2000;18:158PatientswithDTICTemozolomide150療效ORR:overallresponseratePFS:progressionfreesurvivalOS:overallresponseMiddletonMR,etal.JClinOncol2000;18:158療效ORR:overallresponserateMi151毒性和生活質(zhì)量QOL:qualityoflifeMiddletonMR,etal.JClinOncol2000;18:158KiebertGM,etal.CancerInvest2003;21:821毒性和生活質(zhì)量QOL:qualityoflifeMid152化療vs化療聯(lián)合生物治療化療vs化療聯(lián)合生物治療153PatientswithAdvancedMelanoma

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