白蛋白结合型紫杉醇详解.ppt

* * * * * Transcytosis iscompleted when vesiclesare emptied into the subendot囊泡流入内皮下完成胞吞作用 helial space * * * * * * * * * * * * * * * * * Transcytosis iscompleted when vesiclesare emptied into the subendot囊泡流入内皮下完成胞吞作用 helial space * * 溶剂型紫杉醇和ABI-007的半致死量LD50。从肿瘤模型和不携带肿瘤的动物所得到的死亡率数据为X轴，剂量数据为Y轴。使用Bolitzmann sigmoidal equation进行曲线矫正。ABI-007比溶剂型紫杉醇的毒性低，P=0.017（ANOVA） * * * * APPH-1 Slides * 460例MBC随机分二组，纳米白蛋白紫杉醇组Araxane 260mg/m2,静脉滴注30分钟 每3周给药一次， 不需预处理，及泰素紫杉醇 175 mg/m2静脉滴注3小时 每3周给药一次，给予标准预处理 * 纳米白蛋白紫杉醇组及溶剂紫杉醇组一线治疗患者占总患者的比例相似(42% vs. 40%)，ORR二组分别为42% vs 27%，纳米白蛋白紫杉醇明显优于泰素组，在二线治疗中，纳米白蛋白紫杉醇表现同样突出，ORR比溶剂型紫杉醇高一倍，为27% vs. 13%，均有显著统计学差别。 * APPH-1 Slides * 纳米白蛋白紫杉醇显著延长了MBC患者至肿瘤进展时间，白蛋白紫杉醇组TTP为23周，溶剂型紫杉醇组16.9周，相差6.1周，有显著统计学差异。 * APPH-1 Slides * * APPH-1 Slides * 二组发生3度以上感觉神经病变的比例分别为纳米白蛋白紫杉醇组10%，溶剂型紫杉醇组2%，有统计学差异，尤其纳米白蛋白紫杉醇组3度感觉神经病变在中位时间22天即能迅速缓解 * Reference Gradishar et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005; 23: 7794–7803. * * Speaker Notes: 11/2005 – 06/2006: 302 1st line metastatic breast cancer (MBC) patients were accrued and randomized to 4 arms (300 received study drug and were evaluable) Patients who were treated with docetaxel received oral corticosteroid premedication. No premedication was required prior to administration of albumin-bound paclitaxel. All arms received the maximum tolerated dose at schedule except for Arm B. A centralized, independent radiologic assessment was added as an amendment to the protocol. * APPH-1 Slides * * * The most common treatment-emergent AEs were neutropenia, sensory neuropathy, fatigue, alopecia, and arthralgia. Grade 4 neutropenia was reported significantly more frequently in patients who received the docetaxel regimen compared with all 3 nab-paclitaxel arms (P .001). Incidence of sensory neuropathy was comparable between docetaxel and all 3 nab-paclitaxel regimens (P .1 for all 3 comparis