乳腺癌节拍化疗

节拍化疗在乳腺癌中的应用,节拍化疗 vs 传统化疗,节拍化疗：小剂量化疗药、频繁、规律给药传统化疗：最大耐受剂量、每3周间隔给药,传统化疗,节拍化疗,Metronomic Chemotherapy- a Multi-targeted Chemotherapy,Number of published papers over the years,Number of published papers according to country/region,节拍化疗在乳腺癌中的应用,晚期乳腺癌 ： 姑息化疗，尤其是老人、多线治疗患者早期乳腺癌 ：辅助化疗/新辅助化疗,Metronomic Drug,CyclophosphamideMethotrexateFluorouracil : FT207/UFT/CapecitabineEtoposideVinorelbineTemozolomideTaxanespegylated liposomal doxorubicinIrinotecanCisplatin,口服便宜耐受好,Metronomic Schedule,Pure metronomic chemotherapyMetronomic chemotherapy + Hormonal therapyMetronomic chemotherapy + Targeted therapyMetronomic chemotherapy + Tmmunologic agentsMetronomic chemotherapy + Drug repositioning,Ongoing Pure metronomic studies,Metronomic Chemotherapy and Hormonal Therapy,SERD: Tamoxifen/ ToremifeneAromotase inhibitorFulvestrant,1477 post menopausal HR positive BC patients,激素受体阳性的绝经后乳腺癌患者，化疗与他莫西芬同时使用差于序贯使用,绝境前女性化疗可否与他莫昔芬联合使用？其他内分泌药物可否与化疗同时使用？ 芳香化酶抑制剂？ 氟维司群？,Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide As Primary Systemic Treatment in Elderly Breast Cancer Patients,CR + PR = ORR,40.3%+ 31.6%=71.9%,43.8%+43.8%=87.6%,J Clin Oncol,2006,Other Trials,Ongoing Trials,Metronomic Chemotherapy and Targeted Therapy,Ongoing Trials,Metronomic Chemotherapy and Immunologic Agents,Metronomic Chemotherapy and Drug Repositioning,Other 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 polymorphismsCirculating endothelial progenitor cells (CEP)Thrombospondin-1 (TSP-1)THBS1212 (endogenous angiogenesis inhibitor )Macrocytosis (mean corpuscular volume 100