胃癌NCCN指南新进展-脂质体阿霉素.pptVIP

* 楷莱? 和传统多柔比星的对比 半衰期延长 ( 55 小时) 每月一次给药就可以有持续输注相同的效果 延长的肿瘤暴露可以对抗血浆中多药耐药(MDR)基因的表达 安全性改善 没必要使用中央插管 中性粒细胞减少症和贫血发生率更低，因此减少了细胞生长因子等支持治疗的使用 脱发症发生率显著降低 更低的心脏毒性 楷莱 (聚乙醇化的脂质体多柔比星) Hussein MA, et al. Cancer 2002;95(10):2160-8; Gordon AN, et al. J Clin Oncol 2001;19(14):3312-22.; O’Brien MER, et al. Ann Oncol 2004;15(3):440-9.; Alberts DS, et al. Semin Oncol 2004;53-90.; Vail DM, et al Semin Oncol 2004;16-35. 传统多柔比星 脂质体 聚乙烯乙二醇 XBCA0251-09134-5 XBCA0192-08325-9 O’Brien – 心脏毒性事件发生比例Cardiac Event Rates 100 90 80 70 60 50 40 30 20 10 0 0 50 100 150 200 300 250 400 450 500 550 600 350 累积蒽环类药物剂量 (mg/m2) Kaplan-Meier Estimates of Cardiac Event Rate CAELYX? 传统多柔比星 风险比= 3.16 (95% CI: 1.58 - 6.31); P .001 O’Brien et al. Ann Oncol 2004; 15:440-449. . CAELYX? 在实体肿瘤部位的富集 肿瘤部位毛细血管 毛细血管内皮组织 肿瘤细胞 包含有药物 的脂质体(CAELYX??) Adapted from CAELYX? PI, http://CAELYX.com/common/prescribing_information/CAELYX/PDF/CAELYX_PI_Booklet.pdf - Accessed 10-27-08 * OBJECTIVE: Review the Accumlation of CAELYX and its extravasation in solid tumors DISCUSSION POINTS: 1.The development of tumor vasculature is known as angiogenesis. 2.Unlike normal vasculature, these vessels are very permeable (or leaky) with 100 to 800 nm gaps. This allows extravasation of plasma components into the tumor due to a high demand for energy because of the accelerated cellular growth rate of the tumor cells. Because of CAELYX’s longer circulation time, liposomes are distributed and degraded at the tumor site, slowly releasing doxorubicin. 3.The degradation is thought to be due to either a concentration gradient or local enzymes, and is catalyzed by the ammonium sulfate component. Doxorubicin is released and is then able to enter the tumor interstitial fluid. Clinical scenario: Chemosensitivity assay (e.g. Oncotech) usefulness is limited as the tumor environment in vitro cannot duplicate that required for doxorubicin release from the liposomes in vivo. Allen TM and Martin FJ. Advantages of Liposomal Delivery Systems for Anthracyc