乳腺癌节拍化疗

1、 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 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 Cyclophosphamide Methotrexate Fluorouracil : FT207/UFT/Capecitabine Etoposide Vinorelbine Temozolomide Taxanes pegylated liposomal doxorubicin Irinotecan Cisplatin 口服口服 便宜便宜 耐受好耐受好 Pure metronomic chemothe

2、rapy Metronomic chemotherapy + Hormonal therapy Metronomic chemotherapy + Targeted therapy Metronomic chemotherapy + Tmmunologic agents Metronomic chemotherapy + Drug repositioning Author and yearN patientsTreatmentPhasePrevious treatment and setting O R R (%) CB (%)OS (months) Colleoni 200263Cyclop

3、hosphamide+MethotrexateIIPretreated MBC1931.7%/ Orlando 2006153Cyclophosphamide+MethotrexateRetrospectivePretreated MBC/15.7% with CB12 m / Orlando 200622Cyclophosphamide+Methotrexate/Pretreated MBC1846/ Miscoria 201262Cyclophosphamide+MethotrexateIIPretreated MBC/7.1 Perroud 201315Cyclophosphamide+

4、MethotrexateII/6.746.7/ Smith 201033Oral fluorouracilIINot Pretreated MBC55 Tagushi 201033Capecitabine IINot Pretreated MBC184424.8 Fedele 201260CapecitabineIIPretreated MBC246217 Dellapasqua 200846Cyclophosphamide+Capecitabine/Pretreated MBC4868/ Wang 201268Capecitabine+CyclophosphamideIIPretreated

5、 MBC30.35316.9 Yoshimoto 201251Capecitabine+CyclophosphamideIIPretreated MBC4457.8/ Montagna 201224Capecitabine+CyclophosphamideIINot Pretreated MBC6275/ Addeo 201034VinorelbineIINot Pretreated MBC38 15.9 Saridaki 201235Vinorelbine+CapecitabineIPretreated MBC46/ Cazzaniga 201412 + 22Vinorelbine+Cape

6、citabineIIIPretreated MBC/58/ Otsuka 201340Irinotecan+Tegafur/47/26 Dellapasqua 201129L i p o s o m a l d o x o r u b i c i n +cyclophosphamide /Not pretreated Locally advanced 69/ SchedulephaseSetting Ref. Capecitabine 1000 m/m2 d1 14 + VNB 60 mg/m2 d1,8 q21d vs. VNB 50 mg/d d1,3,5/wk II Randomized

7、 M+, 2 cm any N TN or inflammatory NCT01329627 DDP 25 mg/m2 d1 3 q3w +CTX 150 mg/d os d1 14IIM+, TNNCT01910870 TXT 75 mg/m2 + CTX 50 mg/d _ 21 d, q3wIIM+NCT01526499 Capecitabine 1500 mg/d + CTX 50 mg/dIIM+, HER-2 negNCT01526512 Capecitabine 700 mg/m2 bid, d1 14 + Etoposide 30 mg/m2/d, d1 7 q3w IIM+N

8、CT01589159 SERD: Tamoxifen/ Toremifene Aromotase inhibitor Fulvestrant 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？ CR + PR = ORR 40.3%+ 31.6%=71.940.3%+ 31.6%=71.9% 43.8%+43.8%=87.6%43.8%+43.8%=87.6% J Clin Oncol

9、,2006 Author and year N patientsTreatmentPhasePrevious treatment and setting ORR (%) CB (%) OS (months) Aurilio 201233 (22 evaluable for response) Cyclophosphamide Methotrexate Fulvestrant Retrospective Pretreated MB 56 43.6 Schwartzberg 2013 41Capecitabine Fulvestrant II Pretreated MB 24.458.128.6

10、schedulephaseSetting Ref. AI + CM + PDN vs. CM + PDNIIM+, ER+, postmenopausal AI resistance NCT00687648 Capecitabine +AIIIER+, postmenopausal Neoadjuvant Anastrozole +Cap M+ Letrozole resistance: Exemestance+Cap Exemestane resistance: Letrozole+Cap NCT01924078 Anastrozole + tegafur-uracil vs. Anastr

11、ozole IIEarly stage T2N0/1M0 ER+, postmenopausal Neoadjuvant NCT01262274 Author and yearN patientsTreatmentPhasePrevious treatment and setting ORR (%)CB (%)OS (months Orlando 2006 2012 22Cyclophosphamide Methotrexate Trastuzumab IIPretreated MBC1846 Dellapasqua 200846Cyclophosphamide Capecitabine Be

12、vacizumab IIPretreated MBC4868 Garcia-Saenz 2008 24Cyclophosphamide Capecitabine Bevacizumab IIPretreated MBC31.863.613.9 Montagna 201224Cyclophosphamide Capecitabine Bevacizumab IINot Pretreated MBC 6275 Saloustros 201113Vinorelbine Bevacizumab IIPretreated MBC7.7 Montagna 2012 24Erlotinib + bevaci

13、zumab + capecitabine I/II Pretreated MBC6283 schedulephaseSetting Ref. Pertuzumab + Trastuzumab + CTX 50 mg/d?T-DM1 (if PD) IIMBC, HER-2 pos, 60 yrsNCT01597414 Weekly Paclitaxel+ Trastuzumab -Weekly Doxorubicin + Oral CTX Plus Weekly Trastuzumab IIHER2+ Locally Advanced BCNCT01329640 Vinorelbine Met

14、ronomic +Lapatinib IIHER-2+ MBCNCT00754702 Capecitabine+CTX+Lapatinib +Trastuzumab IIHER-2+ MBCNCT01873833 Bevacizumab + PTX vs. Bevacizumab + CTX 50 + capecitabine IIIM+, locally advanced BCNCT01131195 Metronomic CTX+MTX BevacizumabIIMBCNCT00083031 Vinorelbine Metronomic +Bevacizumab IIMBCNCT006942

15、00 Aflibercept + Capecitabine IMBCNCT01843725 Letrozole + Metronomic CTX+ Plus/Minus Sorafenib IIMBCNCT00954135 Author and year N TreatmentPhasePrevious treatment and setting ORR (%)CB (%) Colleoni 2005 171Cyclophosphamide M e t h o t r e x a t e thalidomide Randomized IIPretreated MBC 20.9 vs. 11.8

16、4 1 . 5 v s 41.5 S o r i a n o , J.2011 21cyclophosphamide + methotrexate Vaccine RetrospectivePretreated MBC 2462 Author and year N patientsTreatmentPhasePrevious treatment and setting ORR (%)CB (%) Young 201269Docetaxel Capecitabine Celecoxib RetrospectivePretreated and not MBC Perroud 2013 15Cycl

17、ophosphamide Methotrexate Celecoxib IIPretreated MBC 6.746.7 SchedulephaseSetting 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 IINeoADJ, TNNCT00542191 CTX+MTX+ AspirinIINeoADJNCT01612247 Metformin （二甲双胍） propranolol （普荼洛尔） 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