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1惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022概述好發(fā)于白色人種，我國的發(fā)病率并不高1惡性黑色素瘤專題醫(yī)學(xué)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(xué)致癌物質(zhì)免疫缺陷2惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022發(fā)病因素紫外線照射2惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/2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

2、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3惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022臨床表現(xiàn)雀斑型 占10-15%3惡性黑色素瘤專題醫(yī)學(xué)知識宣臨床表現(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(dāng)病灶繼續(xù)生長時(shí)其顏色變成藍(lán)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(gè)過程輻射生長期的病灶鑲嵌棕黃

3、、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(shí)處理，病灶呈結(jié)節(jié)狀隆起，提示進(jìn)入垂直生長期，淋巴結(jié)轉(zhuǎn)移率增加，預(yù)后差4惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022臨床表現(xiàn)結(jié)節(jié)型 占12%左右4惡性黑色素瘤專題醫(yī)學(xué)知識宣講鏡下腫瘤浸潤深度5惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022鏡下腫瘤浸潤深度5惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/20ClarkI: 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

4、, III/IV缺乏衡量標(biāo)準(zhǔn))6惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022ClarkI: 腫瘤局限于表皮的基底膜內(nèi) (原位黑色素瘤)6Breslow目鏡測微器直接測量腫瘤厚度估計(jì)預(yù)后 0.75 mm 0.761.5 mm 1.514.00 mm 4.00 mm亦有其他分檔7惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Breslow目鏡測微器直接測量腫瘤厚度7惡性黑色素瘤專題醫(yī)AJCC StagingAmerican Joint Committee on Cancer8惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022AJCC StagingAmerican Joint ComTNM分期該領(lǐng)域

5、主要的進(jìn)展AJCC的新的分期系統(tǒng)前哨淋巴結(jié)活檢的應(yīng)用I期至III期的局限性惡黑分期中主要的進(jìn)展有Breslow腫瘤厚度和有否潰瘍應(yīng)用于T分期Clark分期僅應(yīng)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(yīng)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9惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022TNM分期該領(lǐng)域主要的進(jìn)展9惡性黑色素瘤專題醫(yī)學(xué)知識宣講1010惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/202210惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/202211惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/202211惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/202212惡性黑色素瘤專

6、題醫(yī)學(xué)知識宣講10/6/202212惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/2022生存曲線Balch CM, et al. J Clin Oncol 2001; 19:363513惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022生存曲線Balch CM, et al. J Clin On預(yù)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(yuǎn)處轉(zhuǎn)移血LDH水平14惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022預(yù)后因素原發(fā)病灶14惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/2淋巴結(jié)陽性數(shù)目Balch CM, et al. J Clin Oncol 2001; 19:362215惡性黑色素瘤專題醫(yī)學(xué)知

7、識宣講10/6/2022淋巴結(jié)陽性數(shù)目Balch CM, et al. J Clin轉(zhuǎn)移部位Balch CM, et al. J Clin Oncol 2001; 19:362216惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022轉(zhuǎn)移部位Balch CM, et al. J Clin On輔助治療化療無益處生物治療和化療聯(lián)合等待 SWOG 0008 (HD-IFN-CVD)免疫治療17惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助治療化療17惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/202輔助免疫治療高劑量 IFN-低劑量 IFN-IL-2TretinoinGM-CSF腫瘤疫苗18惡性黑色素瘤專

8、題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療高劑量 IFN-18惡性黑色素瘤專題醫(yī)學(xué)知識宣輔助免疫治療高劑量 IFN-低劑量 IFN-IL-2TretinoinGM-CSF腫瘤疫苗19惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療高劑量 IFN-19惡性黑色素瘤專題醫(yī)學(xué)知識宣Patients with Stage B/ Melanoma (N = 280)Observation(n = 137)High-dose IFN-(n = 143)ECOG 1684Kirkwood JM, et al. J Clin Oncol 1996; 14:71Regimen:20 MU/m2 IV

9、 5 days/week 4 weeks10 MU/m2 SC TIW 48 weeks20惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with ObservationHigh-療效IFN-ObservationP value (one-sided)5-y RFS (%)37260.00235-y OS (%)46370.0237RFS: Relapse-free survivalOS: Overall survivalKirkwood JM, et al. J Clin Oncol 1996; 14:7121惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN-Obs

10、ervationP value (one毒性治療延遲/中斷: 50%/度毒性: 76%危及生命毒性: 9%2 例患者因肝功能衰竭死亡Kirkwood JM, et al. J Clin Oncol 1996; 14:7122惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性治療延遲/中斷: 50%Kirkwood JM, et ECOG 1690Observation(n=212)Low-dose IFN-(n=215)High-dose IFN-(n=215)Patients with Stage B/ Melanoma (N = 642)Regimen (Low-dose IFN-):3

11、MU/d SC TIW 2 yearsKirkwood JM, et al. J Clin Oncol 2000; 18:244423惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022ECOG 1690ObservationLow-dose I療效ObservationLD IFN-HD IFN-P value5-y RFS (%)354044*0.0545-y OS (%)555352NSRFS: Relapse-free survivalOS: Overall survivalKirkwood JM, et al. J Clin Oncol 2000; 18:244424惡性黑色素瘤專題醫(yī)學(xué)知

12、識宣講10/6/2022療效ObservationLD IFN-HD IFN-P毒性Kirkwood JM, et al. J Clin Oncol 2000; 18:244425惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性Kirkwood JM, et al. J Clin OPatients with Stage B/ Melanoma (N = 880)GMK vaccine(n = 440)High-dose IFN-(n = 440)ECOG 1694Kirkwood JM, et al. J Clin Oncol 2001; 19:2370Regimen:20 MU/m2 I

13、V 5 days/week 4 weeks10 MU/m2 SC TIW 48 weeks26惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with GMK vaccineHigh-療效IFN-GMK vaccineP value5-y RFS (%)62490.00275-y OS (%)78730.0147RFS: Relapse-free survivalOS: Overall survivalKirkwood JM, et al. J Clin Oncol 2001; 19:237027惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN-GMK vaccineP

14、 value5-y REORTC 18952Observation(n=279)Intermediate-dose IFN-(n=553)High-dose IFN-(n=556)Patients with Stage B/ Melanoma (N = 1388)Regimen (IFN-):10 MU/m2 IV 5 days/week 4 weeks10 MU/d SC TIW 1 years or 5 MU/d SC TIW 2 yearsEggermont, AM, et al. Lancet 2005; 366:118928惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022EORTC 1

15、8952ObservationIntermed療效ObservationIM IFN-HD IFN-P value4.5-y DMFI (%)4047*43#*0.05#0.484.5-y OS (%)485348NSDMFI: distant metastasis free intervalOS: Overall survivalEggermont, AM, et al. Lancet 2005; 366:118929惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效ObservationIM IFN-HD IFN-P毒性Eggermont, AM, et al. Lancet 2005;

16、366:118930惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性Eggermont, AM, et al. Lancet比較ECOG 1684ECOG 1690ECOG 1694EORTC 18952RFS resultpositiveborderlinepositiveborderlineOS resultpositivenegativepositivenegativeStage B (T4N0)11%25%23%26%RFS: Relapse-free survivalOS: Overall survival31惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022比較ECOG 1684EC

17、OG 1690ECOG 1694E輔助免疫治療高劑量 IFN-低劑量 IFN-IL-2TretinoinGM-CSF腫瘤疫苗32惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療高劑量 IFN-32惡性黑色素瘤專題醫(yī)學(xué)知識宣Patients with Node-positive Melanoma (N = 444)Observation(n = 219)Low-dose IFN-(n = 225)WHO 16Cascinelli N, et al. Lancet 2001; 358:866Regimen:3 MU/m2 SC TIW 3 yearsCascinelli N, et al

18、. Lancet 1994; 343:91333惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with ObservationLow-d療效IFN-ObservationP value5-y RFS (%)27.528.40.505-y OS (%)35370.71RFS: Relapse-free survivalOS: Overall survivalCascinelli N, et al. Lancet 1994; 343:913Cascinelli N, et al. Lancet 2001; 358:86634惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN

19、-ObservationP value5-y RPatients with Stage B/ Melanoma (N = 674)Observation(n = 336)Low-dose IFN-(n = 338)UKCCRHancock BW, et al. J Clin Oncol 2004; 22:53Regimen:3 MU/m2 SC TIW 2 years35惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with ObservationLow-d療效IFN-ObservationP value5-y RFS (%)33300.35-y OS (%)46420.6R

20、FS: Relapse-free survivalOS: Overall survivalHancock BW, et al. J Clin Oncol 2004; 22:5336惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN-ObservationP value5-y R輔助免疫治療High-dose IFN-Low-dose IFN-IL-2TretinoinGM-CSFTumor vaccine37惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療High-dose IFN-37惡性黑色素瘤專Patients with T3/4N0M0 Melanoma (N = 22

21、3)Observation(n = 110)Low-dose IFN-+ IL-2(n = 113)德國一項(xiàng)研究Hauschild A, et al. J Clin Oncol 2003; 21:288338惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with ObservationLow-d方案 (IFN-+ IL-2)IFN-3 MU/m2 SC days 1-5 week 1 IL-2 9 MU/m2 SC days 1-4 week 2 IFN-3 MU/m2 SC TIW weeks 3-6 Repeated for 8 cyclesHauschild A, et

22、 al. J Clin Oncol 2003; 21:288339惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案 (IFN-+ IL-2)IFN-3 MU/m2 S療效IFN-+ IL-2ObservationP value5-y RFS (%)70.169.90.935-y OS (%)7774.50.93RFS: Relapse-free survivalOS: Overall survivalHauschild A, et al. J Clin Oncol 2003; 21:288340惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN-+ IL-2ObservationP v

23、alu輔助免疫治療高劑量 IFN-低劑量 IFN-IL-2TretinoinGM-CSF腫瘤疫苗41惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療高劑量 IFN-41惡性黑色素瘤專題醫(yī)學(xué)知識宣Patients with Stage AB Melanoma (N = 407)Low-dose IFN-+ Placebo(n = 201)Low-dose IFN-+ Isotretinoin(n = 206)德國研究Richtig E, et al. J Clin Oncol 2005; 23:865542惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with Low

24、-dose IFN-+ 方案 (IFN-+ Isotrenoin)IFN-3 MU/m2 SC TIW 2 years Isotrenitoin 20mg/30mg QD 2 years (20mg for pts 73kg, 30mg for pts 73kg) Richtig E, et al. J Clin Oncol 2005; 23:865543惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案 (IFN-+ Isotrenoin)Richtig 療效IFN-+ IsotrenoinIFN-+ PlaceboP value5-y RFS (%)55670.255-y OS (%)76

25、810.8RFS: Relapse-free survivalOS: Overall survivalRichtig E, et al. J Clin Oncol 2005; 23:865544惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效IFN-+ IsotrenoinIFN-+ Plac輔助免疫治療高劑量 IFN-低劑量 IFN-IL-2TretinoinGM-CSF腫瘤疫苗45惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022輔助免疫治療高劑量 IFN-45惡性黑色素瘤專題醫(yī)學(xué)知識宣 GM-CSF 腫瘤疫苗 促樹突細(xì)胞的增殖, 成熟和遷移誘導(dǎo)T細(xì)胞介導(dǎo)的 免疫應(yīng)答等待 ECOG 4697

26、 (GM-CSF vs 觀察)無生存益處購買不到等待與其他藥物聯(lián)合 的研究46惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022 GM-CSF 腫瘤疫苗 促樹突細(xì)轉(zhuǎn)移后的治療47惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022轉(zhuǎn)移后的治療47惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/202單藥有效細(xì)胞毒藥物AgentNo. of evaluable patientsORR (%)Decarbazine (DTIC) 1936 20Temozolomide 56 21Carmustine (BCNU) 122 18Lomustine (CCNU) 270 13Fotemustine 153 24Cispl

27、atin 188 23Carboplatin 43 16Vinblastine 62 13Vindesine 273 14Paclitaxel 65 18Docetaxel 26 1548惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022單藥有效細(xì)胞毒藥物AgentNo. of evaluable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)49惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022常用方案單藥49惡性黑色素瘤專題醫(yī)學(xué)知識

28、宣講10/2/202TAM?50惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022TAM?50惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2/2022Patients with Advanced Melanoma (N = 184)DDP + DTIC + BCNU(n = 92)DDP + DTIC + BCNU + TAM(n = 92)NCI StudyCreagan ET, et al. J Clin Oncol 1999; 17:188451惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with DDP + DTIC + BCN方案CDB: DDP + DTIC + BCNUDD

29、P 25mg/m2 days 1-3DTIC 220mg/m2 days 1-3BCNU 150mg/m2 day 1 every other dayDDP + DTIC + BCNU + TAMTAM 20mg QD Repeated every 3 wksCreagan ET, et al. J Clin Oncol 1999; 17:188452惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案CDB: DDP + DTIC + BCNUCreaga療效CDBCDBTP valueORR (%)37320.52TTP (mos)3.43.10.429OS (mos)6.86.90.545

30、ORR: overall response rateTTP: time to progressionOS : overall survivalCreagan ET, et al. J Clin Oncol 1999; 17:188453惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效CDBCDBTP valueORR (%)37320.5單藥 vs 聯(lián)合化療54惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022單藥 vs 聯(lián)合化療54惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/2Patients with Advanced Melanoma (N = 240)DTIC(n = 121)DDP + DTIC

31、 + BCNU + TAM(n = 119)研究設(shè)計(jì)Chapman PB, et al. J Clin Oncol 1999; 17:274555惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with DTICDDP + DTIC +方案DTIC aloneDTIC 1000mg/m2 day 1CDBT: DDP + DTIC + BCNU + TAMDDP 25mg/m2 days 1-3DTIC 220mg/m2 days 1-3BCNU 150mg/m2 day 1 every other cycleTAM 20mg QD Repeated every 3 wksCh

32、apman PB, et al. J Clin Oncol 1999; 17:274556惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案DTIC aloneChapman PB, et al.療效DTICCDBTP valueORR (%)10.218.50.09OS (mos)6.47.70.51ORR: overall response rateOS : overall responseChapman PB, et al. J Clin Oncol 1999; 17:274557惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效DTICCDBTP valueORR (%)10.218毒

33、性 (/度)Chapman PB, et al. J Clin Oncol 1999; 17:274558惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性 (/度)Chapman PB, et al. J DTIC vs Temozolomide59惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022DTIC vs Temozolomide59惡性黑色素瘤專題Patients with Advanced Melanoma (N = 305)DTIC250mg/m2 days 1-5 Q3wks(n = 149)Temozolomide200mg/m2 days 1-5 Q4wks(n = 156)

34、研究設(shè)計(jì)Middleton MR, et al. J Clin Oncol 2000; 18:15860惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with DTICTemozolomide療效DTICTemozolomideP valueORR (%)12.113.5NSPFS (mos)1.51.90.012OS (mos)6.47.70.2ORR: overall response ratePFS: progression free survivalOS : overall responseMiddleton MR, et al. J Clin Oncol 2000;

35、 18:15861惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效DTICTemozolomideP valueORR (毒性和生活質(zhì)量DTICTemozolomideP valueGrade / (%)3638NSCNS metastases-less-QOL-better-QOL: quality of lifeMiddleton MR, et al. J Clin Oncol 2000; 18:158Kiebert GM, et al. Cancer Invest 2003; 21:82162惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性和生活質(zhì)量DTICTemozolomideP

36、 value化療 vs 化療聯(lián)合生物治療63惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022化療 vs 化療聯(lián)合生物治療63惡性黑色素瘤專題醫(yī)學(xué)知識宣講Patients with Advanced Melanoma (N = 282)Temozolomide(n = 139)Temozolomide + IFN-(n = 143)DeCOG StudyKaufmann R, et al. J Clin Oncol 2005; 23:900164惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with TemozolomideTemo方案Temozolomide 單藥200mg/m

37、2 days 1-5 Q4wksTemozolomide + IFN-Temozolomide: 200mg/m2 days 1-5 Q4wksIFN-: 5MU/m2 TIWKaufmann R, et al. J Clin Oncol 2005; 23:900165惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案Temozolomide 單藥Kaufmann R, e療效TemozolomideTemozolomide + IFN-P valueORR (%)13.424.10.036PFS (mos)2.43.30.11OS (mos)8.49.70.16ORR: overall re

38、sponse ratePFS: progression-free survivalOS : overall responseKaufmann R, et al. J Clin Oncol 2005; 23:900166惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效TemozolomideTemozolomide + I毒性 (/度)TemozolomideTemozolomide + IFN-P valueLeucopenia4.3%20.5%0.0001Thrombocytopenia4.3%22.7%0.0001fever0.9%2.5%0.0001OthersComparableNS

39、Kaufmann R, et al. J Clin Oncol 2005; 23:900167惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022毒性 (/度)TemozolomideTemozolom聯(lián)合 IFN + IL-2?68惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022聯(lián)合 IFN + IL-2?68惡性黑色素瘤專題醫(yī)學(xué)知識宣講Patients with Advanced Melanoma (N = 183)CVD(n = 92)CVD + IFN-+ IL-2(n = 91)MDACC StudyEton O, et al. J Clin Oncol 2002; 20:204569惡性黑

40、色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with CVDCVD + IFN-+ 方案CVDDDP 20mg/m2 d1-4, 22-25VLB 2mg/m2 d1-4, 22-25DTIC 800mg/m2 d1, 22 Repeated every 6wksCVD + IFN-+ IL-2DDP 20mg/m2 d1-4, 22-25VLB 1.5mg/m2 d1-4, 22-25DTIC 800mg/m2 d1, 22IFN-5MU/m2 d5-9, 17-21, 26-30IL-2 9MU/m2 d5-8, 17-20, 26-29 Repeated every 6wk

41、s70惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案CVDCVD + IFN-+ IL-270惡性黑色素瘤療效CVDCVD + IFN-+ IL-2P valueORR (%)25480.001TTP (mos)2.44.90.008OS (mos)9.211.90.06ORR: overall response rateTTP: time to progressionOS : overall responseEton O, et al. J Clin Oncol 2002; 20:204571惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022療效CVDCVD + IFN-+ IL-2P va

42、lueO血液學(xué)毒性Eton O, et al. J Clin Oncol 2002; 20:204572惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022血液學(xué)毒性Eton O, et al. J Clin Onc非血液學(xué)毒性Eton O, et al. J Clin Oncol 2002; 20:204573惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022非血液學(xué)毒性Eton O, et al. J Clin OnPatients with Advanced Melanoma (N = 405)CVD(n = 201)CVD + IFN-+ IL-2(n = 204)ECOG 3695Atkins

43、 MB, et al. ASCO 2003; 22:2847a74惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with CVDCVD + IFN-+ 方案CVDDDP 20mg/m2 d1-4VLB 1.2mg/m2 d1-4DTIC 800mg/m2 d1 Repeated every 3wksCVD + IFN-+ IL-2DDP 20mg/m2 d1-4VLB 1.2mg/m2 d1-4DTIC 800mg/m2 d1IFN-5MU/m2 d1-5, 8, 10, 12IL-2 9MU/m2 CIV 96 hours Repeated every 3wksAtkins

44、 MB, et al. ASCO 2003; 22:2847a75惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022方案CVDCVD + IFN-+ IL-2Atkins M療效CVDCVD + IFN-+ IL-2P valueORR (%)11.916.6NSPFS (mos)3.15.00.1OS (mos)9.18.40.696ORR: overall response ratePFS: progression-free survivalOS : overall responseAtkins MB, et al. ASCO 2003; 22:2847a76惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/

45、6/2022療效CVDCVD + IFN-+ IL-2P valueOPatients with Advanced Melanoma (N = 144)CVD(n = 72)CVD + IFN-+ IL-2(n = 72)意大利研究Bajetta E, et al. Ann Oncol 2006; 17:57177惡性黑色素瘤專題醫(yī)學(xué)知識宣講10/6/2022Patients with CVDCVD + IFN-+ 方案CVDDDP 30mg/m2 d1-3VDS 2.5mg/m2 d1DTIC 250mg/m2 d1-3 Repeated every 3wksCVD + IFN-+ IL-2DDP 30mg/m2 d1-3VDS 2.5mg/m2 d1DTIC 250mg