恶性黑色素瘤药物发展.pptx

恶性黑色素瘤药物发展;黑色素瘤治疗靶点;转移潜能;IV期黑色素瘤的III期临床试验(1);Eggermont;IV期黑色素瘤的III期临床试验(1) 化疗+ IL-2 + IFN;黑色素瘤;CTLA4 阻断;抗CTLA-4 单克隆抗体;T细胞受体: MHC抗原;Copyright ?2003 by the National Academy of Sciences;一例进展期黑色素瘤患者Ipilimumab相关性皮疹;1. Attia P, et al. J Clin Oncol. 2005;23:6043-6053.2. Beck K, et al. J Clin Oncol. 2006;24:2283-2289.;1. Robinson et al. J Immunother. 2004;27:478.2. Phan et al. Proc Natl Acad Sci USA. 2003;100:8372.;Blansfield et al. J Immunother. 2005;28:593-598.;;Correlation Between IRAEs and Clinical Response; NCI外科部门 162例患者 有效率 13.8% ABE (自体免疫紊乱事件: 40%) 结肠炎 33% 眼葡萄膜炎 5% 垂体炎 4% ;先前SD变为PR;先前明显PD的患者获得持续的完全缓解;治疗前 12周后 (10/06);III期 (二线) IL2+多肽 vs CTLA-4 + IL2+多肽 III期 (一线) DTIC vs DTIC + Ipilimumab III期 III期辅助治疗 EORTC 18071 : Ipilimumab vs 安慰剂 1000例患者 ;非清髓性淋巴细胞删除化疗后输注过继细胞 治疗难治性转移性黑色素瘤 Mark E. Dudley, John R. Wunderlich, James C. Yang, Richard M. Sherry, Suzanne L. Topalian, Nicholas P. Restifo, Richard E. Royal, Udai Kammula, Don E. White, Sharon A. Mavroukakis, Linda J. Rogers, Gerald J. Gracia, Stephanie A. Jones, David P. Mangiameli, Michelle M. Pelletier, Juan Gea-Banacloche, Michael R. Robinson, David M. Berman, Armando C. Filie, Andrea Abati, Steven A. Rosenberg Journal of Clinical Oncology, Vol 23, No 10 (April 1), 2005: pp. 2346-2357; NCI外科部 51例患者 有效率 51 % 采集浸润性淋巴细胞(TIL) +体外双倍扩增 福达拉滨 + 环磷酰胺 淋巴细胞删除治疗 终点细胞因子维持 TIL输注+ 体内100-1000倍扩增 所有患者均为多种治疗失败，包括高剂量白介素-2;非清髓性淋巴细胞删除化疗后输注过继细胞  治疗难治性转移性黑色素瘤;非清髓性淋巴细胞删除化疗后输注过继细胞  治疗难治性转移性黑色素瘤;Metastaticpotential;BAY 43-9006 Sorafenibsuccess inRCCHCCin Stage IV Melanoma;BRAF in melanoma;BAY 43-9006;BAY 43-9006, carboplatin & paclitaxelStudy schema;BAY 43-9006, carboplatin & paclitaxelResponses in relation to prior therapy and stage;BAY 43-9006 is well tolerated with full doses of carboplatin & paclitaxel No evidence of additive toxicities or PK interactions Antitumor activity in metastatic melanoma patients Durable partial responses, all l