乳腺癌节拍化疗

1、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 ChemotherapyNumber of published papers over the yearsNumber 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 DrugCyclophosph

2、amideMethotrexateFluorouracil : FT207/UFT/CapecitabineEtoposideVinorelbineTemozolomideTaxanespegylated liposomal doxorubicinIrinotecanCisplatin口服口服便宜便宜耐受好耐受好Metronomic Schedule Pure metronomic chemotherapyMetronomic chemotherapy + Hormonal therapyMetronomic chemotherapy + Targeted therapyMetronomic

3、chemotherapy + Tmmunologic agentsMetronomic chemotherapy + Drug repositioningAuthor and yearN patientsTreatmentPhasePrevious treatment andsettingO R R (%)CB (%)OS(months)Colleoni 200263Cyclophosphamide+MethotrexateIIPretreated MBC1931.7%/Orlando 2006153Cyclophosphamide+MethotrexateRetrospectivePretr

4、eated MBC/15.7% withCB12 m/Orlando 200622Cyclophosphamide+Methotrexate/Pretreated MBC1846/Miscoria 201262Cyclophosphamide+MethotrexateIIPretreated MBC/7.1Perroud 201315Cyclophosphamide+MethotrexateII/6.746.7/Smith 201033Oral fluorouracilIINot Pretreated MBC55 Tagushi 201033Capecitabine IINot Pretrea

5、ted MBC184424.8Fedele 201260CapecitabineIIPretreated MBC246217Dellapasqua 200846Cyclophosphamide+Capecitabine/Pretreated MBC4868/Wang 201268Capecitabine+CyclophosphamideIIPretreated MBC30.35316.9Yoshimoto 201251Capecitabine+CyclophosphamideIIPretreated MBC4457.8/Montagna 201224Capecitabine+Cyclophos

6、phamideIINot Pretreated MBC6275/Addeo 201034VinorelbineIINot Pretreated MBC38 15.9Saridaki 201235Vinorelbine+CapecitabineIPretreated MBC46/Cazzaniga 201412 + 22Vinorelbine+CapecitabineIIIPretreated MBC/58/Otsuka 201340Irinotecan+Tegafur/47/26Dellapasqua 201129L i p o s o m a l d o x o r u b i c i n

7、+cyclophosphamide/Not pretreatedLocally advanced69/Ongoing Pure metronomic studies SchedulephaseSetting Ref.Capecitabine 1000 m/m2 d1 14 + VNB 60 mg/m2 d1,8 q21d vs. VNB 50 mg/d d1,3,5/wkIIRandomizedM+, 2 cm any N TN or inflammatoryNCT01329627DDP 25 mg/m2 d1 3 q3w +CTX 150 mg/d os d1 14IIM+, TNNCT01

8、910870TXT 75 mg/m2 + CTX 50 mg/d _ 21 d, q3wIIM+NCT01526499Capecitabine 1500 mg/d + CTX 50 mg/dIIM+, HER-2 negNCT01526512Capecitabine 700 mg/m2 bid, d1 14 +Etoposide 30 mg/m2/d, d1 7 q3wIIM+NCT01589159Metronomic Chemotherapy and Hormonal TherapySERD: Tamoxifen/ ToremifeneAromotase inhibitorFulvestra

9、nt1477 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 PatientsCR + PR

10、 = ORR40.3%+ 31.6%=71.940.3%+ 31.6%=71.9%43.8%+43.8%=87.6%43.8%+43.8%=87.6%J Clin Oncol,2006Other Trials Author and yearN patientsTreatmentPhasePrevious treatment andsettingORR (%) CB (%) OS(months)Aurilio 201233 (22 evaluable forresponse)CyclophosphamideMethotrexateFulvestrantRetrospective Pretreat

11、edMB56 43.6Schwartzberg201341CapecitabineFulvestrantII PretreatedMB24.458.128.6Ongoing Trials schedulephaseSetting Ref.AI + CM + PDN vs. CM + PDNIIM+, ER+, postmenopausalAI resistanceNCT00687648Capecitabine +AIIIER+, postmenopausalNeoadjuvant Anastrozole +CapM+ Letrozole resistance: Exemestance+CapE

12、xemestane resistance: Letrozole+CapNCT01924078Anastrozole + tegafur-uracil vs. AnastrozoleIIEarly stage T2N0/1M0ER+, postmenopausalNeoadjuvantNCT01262274Metronomic Chemotherapy and Targeted TherapyAuthor and yearN patientsTreatmentPhasePrevious treatment andsettingORR (%)CB (%)OS(monthsOrlando 20062

13、01222CyclophosphamideMethotrexateTrastuzumabIIPretreated MBC1846 Dellapasqua 200846CyclophosphamideCapecitabineBevacizumabIIPretreated MBC4868 Garcia-Saenz200824CyclophosphamideCapecitabineBevacizumabIIPretreated MBC31.863.613.9Montagna 201224CyclophosphamideCapecitabineBevacizumabIINot Pretreated M

14、BC6275 Saloustros 201113VinorelbineBevacizumabIIPretreated MBC7.7 Montagna201224Erlotinib + bevacizumab + capecitabine I/II Pretreated MBC6283 Ongoing TrialsschedulephaseSetting Ref.Pertuzumab + Trastuzumab + CTX 50 mg/d?T-DM1 (if PD)IIMBC, HER-2 pos, 60 yrsNCT01597414Weekly Paclitaxel+ Trastuzumab

15、-Weekly Doxorubicin + Oral CTX Plus Weekly Trastuzumab IIHER2+ Locally Advanced BCNCT01329640Vinorelbine Metronomic +Lapatinib IIHER-2+ MBCNCT00754702Capecitabine+CTX+Lapatinib +Trastuzumab IIHER-2+ MBCNCT01873833Bevacizumab + PTX vs. Bevacizumab + CTX 50 + capecitabine IIIM+, locally advanced BCNCT

16、01131195Metronomic CTX+MTX BevacizumabIIMBCNCT00083031Vinorelbine Metronomic +Bevacizumab IIMBCNCT00694200Aflibercept + Capecitabine IMBCNCT01843725Letrozole + Metronomic CTX+ Plus/Minus Sorafenib IIMBCNCT00954135Metronomic Chemotherapy and Immunologic AgentsAuthor and yearN TreatmentPhasePrevious t

17、reatment andsettingORR (%)CB (%)Colleoni 2005 171CyclophosphamideM e t h o t r e x a t e thalidomideRandomized IIPretreatedMBC20.9 vs. 11.84 1 . 5 v s 41.5S o r i a n o , J.201121cyclophosphamide + methotrexateVaccineRetrospectivePretreatedMBC2462Metronomic Chemotherapy and Drug RepositioningAuthor

18、and yearN patientsTreatmentPhasePrevious treatment andsettingORR (%)CB (%)Young 201269DocetaxelCapecitabineCelecoxibRetrospectivePretreated and not MBC Perroud 2013 15CyclophosphamideMethotrexateCelecoxibIIPretreatedMBC6.746.7SchedulephaseSetting 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 + digoxinIINeoADJ, TNNCT00542191CTX+MTX+ AspirinIINeoADJNCT01612247Other 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 C