乳腺癌节拍化疗 课件.ppt

Metronomic Chemotherapy and Drug Repositioning Author and year N patients Treatment Phase Previous treatment and setting ORR (%) CB (%) Young 2012 69 Docetaxel Capecitabine Celecoxib Retrospective Pretreated and not MBC ? ? Perroud 2013 15 Cyclophosphamide Methotrexate Celecoxib II Pretreated MBC 6.7 46.7 Schedule phase Setting Ref. DOX 24 mg/m2 + CTX 60 mg/m2 os/wk ×12 --PTX 80 mg/m2 + CBDCA AUC 2/wk -12 Capecitabine 1000 mg/d + digoxin II NeoADJ, TN NCCTX+MTX+ Aspirin II NeoADJ NCOther Repositioning Drugs Metformin （二甲双胍） propranolol （普荼洛尔） 节拍化疗存在的问题 传统MTD的化疗模式“根深蒂固” 节拍化疗概念模糊，用药剂量、频次、间隔不清晰 经验用药，缺少Ⅲ期随机对照研究的证据； 缺少可靠的疗效预测指标 PK/PD Driven Metronomics Biomarker of Metronomic Chemotherapy Plasma VEGF and VEGF gene polymorphisms Circulating endothelial progenitor cells (CEP) Thrombospondin-1 (TSP-1) THBS?1212 (endogenous angiogenesis inhibitor ) Macrocytosis (mean corpuscular volume 100 fl) HIF?1α Immune factors:TREG cells 口服长春瑞滨节拍化疗对比常规化疗的疗效和安全性研究 生物标志物的检测：血管生成指标、免疫指标 血药浓度监测 谢谢! * * * * * * * * * * 114 elderly T2-4 N0-1 ER+ breast cancer patients positive breast cancer were randomly assigned to primary letrozole therapy (2.5 mg daily for 6 months) or a combination of letrozole plus oral cyclophosphamide (50 mg/daily for 6 months) in an open-labeled, randomized phase II trial. Overall response rate was 71.9% (95% CI, 60.0 to 83.8) in the 57 patients randomly assigned to receive primary letrozole and 87.7% (95% CI, 78.6 to 96.2) in the 57 patients randomly assigned to receive letrozole plus cyclophosphamide. * * * It has previously been shown that the metronomic CM combination leads to a marked decrease in circulating VEGF [9]. Moreover, experimental studies suggest that neutralizing antibodies against HER2 or epidermal growth factor receptor (EGFR) result in down-regulation of angiogenesis, through VEGF gene suppression * * * * * * * Vinorelbine is a semi-synthetic vinca-alcaloid that targets tubulin. Binding to tubulin prevents tumor cell f