新竹馬偕紀念醫院癌症中心 乳癌化學治療藥物處方

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1 新竹馬偕紀念醫院癌症中心 乳癌化學治療藥物處方 文件修訂記錄 修正次數 修正日期 修正版別 修 改 內 容 初次訂定 修訂 修訂 :Triple-Negative Breast Cancer 處方 新增 :Neoadjuvant-p7~ 修訂 :FEC + Trastuzumab P.8 0

2 Mackay Memorial Hospital Practical Guideline In Breast Cancer: Adjuvant Setting 2013 V03 Non-trastuzumab containing regimens Low risk disease: Node negative and all of the following features: pt <=2 cm, Grade 1, no vascular invasion, HER2(-), ER and/or PgR expressed (highly endocrine responsive and incompletely endocrine responsive), Age>=35 years Recommendation: endocrine therapy. Options: 1.CMF x 6 if pt >1cm. 2. FE(75)C x 6 if pt >1cm CMF CivMF [1] CEF Cyclophosphamide 600 mg/m2 day 1 Methotrexate 40 mg/m2 IV day 1 5-Fluorouracil 600 mg/m2 IV day 1 Repeat cycle every 21 days for a total of 6 cycles CMF IV high dose : NEAT/BR9601 trial[2] Cyclophosphamide 750 mg/m2 day 1 Methotrexate 50 mg/m2 IV day 1 5-Fluorouracil 600 mg/m2 IV day 1 Repeat cycle every 21 days for a total of 6 cycles CMF (Bonadonna regimen)[3] Cyclophosphamide 100mg/m PO days 1-14 Methotrexate 40 mg/miv days 1 & 8 5-Fluorouracil 600 mg/m IV days 1 & 8 Repeat cycle every 28 days for a total of 6 cycles CEF (low dose) 5-Fluorouracil: 500 mg/m 2 IV day 1 Epirubicin: 75 mg/m 2 IV day 1 Cyclophosphamide: 500 mg/m 2 IV day 1 Repeat cycle every 21 days for a total of 6 cycles Intermediate risk and node negative disease: Node negative and at least one of the following features: pt >2 cm, Grade 2-3, vascular invasion, HER2(-), ER and PgR absent, age <35 years Recommendation: adjuvant chemotherapy followed by endocrine therapy if ER and/or PgR expressed CMF CEF CEF (low dose) Intermediate risk and node positive disease: 1 3 nodes positive AND ER and/or PgR expressed 1

3 and HER2(-) Recommendation: adjuvant chemotherapy followed by endocrine therapy Options FE(75-100)C x *taxanes * weekly paclitaxel x 8-12 or tri-weekly docetaxel x 3-4 CMF (Bonadonna regimen) or CMF high dose CEF (Epirubicin 90 except intolerable toxicities) CEF (FASG-05 trial) [4] 5-Fluorouracil: 500 mg/m 2 IV day 1 Epirubicin: 100 mg/m 2 IV day 1 Cyclophosphamide: 500 mg/m 2 IV day 1 Repeat cycle every 21 days for a total of 6 cycles FEC (NCIC MA.5 trial) [5] Cyclophosphamide 75 mg/m 2 PO days 1-14 Epirubicin 60 mg/m 2 IV days 1 & 8 5-Fluorouracil 500 mg/m 2 IV days 1 & 8 Repeat cycle every 28 days for a total of 6 cycles E followed by CMF E followed by CMF [2] # Dosing modifications must be adjusted accordingly to reflect patient s parameters (age; performance status; co-morbid illnesses; and baseline cardiac, hematologic, hepatic, and renal status), as well as any specific drug-induced toxicities that may have been experienced with prior treatment. # FEC: /75-100/ Epirubicin 100 mg/m 2 IV day 1 Cycled every 21 days for 4 cycles Cyclophosphamide 100 mg/m 2 PO days 1-14 Methotrexate 40 mg/m 2 IV days 1 & 8 5-Fluorouracil 600 mg/m 2 IV days 1 & 8 Cycled every 28 days for 4 cycles. OR Cyclophosphamide 750 mg/m 2 IV day 1 Methotrexate 50 mg/m 2 IV day 1 5-Fluorouracil 600 mg/m 2 IV day 1 Cycled every 28 days for 4 cycles FEC followed by docetaxel FEC followed by Docetaxel (PACS 01 trial) [6] 2

4 5-Fluorouracil 500 mg/m 2 IV day 1 Epirubicin 100 mg/m 2 IV day 1 Cyclophosphamide 500 mg/m 2 day 1 Cycled every 21 days for 3 cycles. Docetaxel 100 mg/m 2 day 1 Cycled every 21 days for 3 cycles FEC followed by paclitaxel FEC followed by paclitaxel (GEICAM 9906 trial)[7] 5-Fluorouracil 600 mg/m 2 IV day 1 Epirubicin 90 mg/m 2 IV day 1 Cyclophosphamide 600 mg/m 2 day 1 Cycled every 21 days for 4 cycles Paclitaxel 100 mg/m by 1 h IV weekly for 8 weeks AC followed by paclitaxel AC followed by paclitaxel (E1199 trial)[8] Doxorubicin 60 mg/m 2 IV day 1 Cyclophosphamide 600 mg/m 2 IV day 1 Cycled every 21 days for 4 cycles. Paclitaxel 175 mg/m 2 by 3 h IV day 1 Cycled every 21 days for 4 cycles[9] OR Paclitaxel 80 mg/m by 1 h IV weekly for 12 weeks TC (USOG 9735) TC regimen[10] Docetaxel 75 mg/m 2 IV day 1 Cyclophosphamide 600 mg/m 2 IV day 1 every 3 wks x 4 cycles High risk disease: 1 3 nodes positive AND ER and PgR absent >3 nodes positive Recommendation: adjuvant chemotherapy followed by endocrine therapy if ER and/or PgR expressed FEC followed by docetaxel FEC followed by paclitaxel AC followed by paclitaxel TC (USOG 9735) TAC TAC (BCIRG 001) [11] Doxetaxel 75 mg/m 2 IV days 1 Doxorubicin 50 mg/m 2 IV day 1 3

5 Dose-dense AC followed by paclitaxel (C 9741) Dose Dense A-T-C (C9741) Triple-Negative Breast Cancer Cyclophosphamide 500 mg/m 2 IV day 1 Cycled every 21 days for 6 cycles (All cycles are with filgrastim support) Dose-dense AC followed by paclitaxel [12] Doxorubicin 60 mg/m 2 IV day 1 Cyclophosphamide 600 mg/m 2 IV day 1 Cycled every 14 days for 4 cycles. Paclitaxel 175 mg/m 2 by 3 h IV day 1 Cycled every 14 days for 4 cycles Dose-dense A-T-C [12] Doxorubicin 60 mg/m 2 IV day 1 Cycled every 14 days for 4 cycles Paclitaxel 175 mg/m 2 by 3 h IV day 1 Cycled every 14 days for 4 cycles Cyclophosphamide 600 mg/m 2 IV day 1 Cycled every 14 days for 4 cycles. (All cycles are with filgrastim support). Recommendation: adjuvant chemotherapy as regimens for high risk breast cancer Options: TC (USOG 9735) FEC (high dose) x 4 + cisplatin (75 mg/m2 q3w) x 4, 或 FEC (high dose) x 4 + Taxotere (75 mg) x 4 Taxanes + cisplatin x 4 followed by CEF x 4 (node positive) Cisplatin Options of adjuvant chemotherapy for triple negative breast cancer Weekly: 30 mg/m 2 75 mg/m 2 q3w (REF: Neoadjuvant Cisplatin trial: Garber JE et al., SABCS 2006 abstract 3074) HER2 (+) Breast Cancer 起健保給付 Node postive 患者 Trastuzumab 作為 Adjuvant therapy 4

6 TRASTUZUMAB CONTAINING COMBINATIONS Consider clinical trials Preferred Adjuvant Regimen: AC(FEC) T + concurrent trastuzumab: Docetaxel + trastuzumab FEC TCH (docetaxel, carboplatin, trastuzumab) Chemotherapy followed by trastuzmab sequentially AC followed by T chemotherapy with Trastuzumab Chemotherapy followed by trastuzumab (HERA trial) Docetaxel + Trastuzumab followed by FEC (FinHer trial) AC followed by TH[13-15] Doxorubicin 60 mg/m 2 / Cyclophosphamide 600 mg/m 2 IV day 1 Cycled every 21 days for 4 cycles. Paclitaxel 175 mg/m 2 by 3 h IV day 1 OR Docetaxel 100 mg/m 2 by 3 h IV day 1 Cycled every 21 days for 4 cycles OR Paclitaxel 80 mg/m by 1 h IV weekly for 12 wks With Trastuzumab 4 mg/kg IV with first dose of paclitaxel Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment. Trastuzumab 6 mg/kg IV every 3 wk may be used following the completion of paclitaxel, and given to complete 1y of trastuzumab treatment. #Cardiac monitoring at baseline, 3, 6, and 9 mo.[14] Chemotherapy followed by trastuzumab[16] Approved adjuvant chemotherapy regimen for at least 4 cycles Trastuzumab 8 mg/kg IV times 1 dose Trastuzumab 6 mg/kg IV every 21 days for 1 y Cardiac monitoring at baseline, 3, 6, and 9 mo. Docetaxel + trastuzumab followed by FEC[17] Docetaxel 100 mg/m 2 by 1 h IV day 1 Cycled every 21 days for 3 cycles With Trastuzumab 4 mg/kg IV with first dose of docetaxel day 1 5

7 Trastuzumab 2 mg/kg IV weekly to complete 9 weeks of trastuzumab. 5-Fluorouracil 600 mg/m 2 IV day 1 Epirubicin 60 mg/m 2 day 1 Cyclophosphamide 600 mg/m 2 day 1 Cycled every 21 days for 3 cycles # Cardiac monitoring at baseline, after last FEC cycle, at 12 and 36 mo after TCH (docetaxel, carboplatin, trastuzumab) chemotherapy. TCH (docetaxel, carboplatin, trastuzumab)[15] Docetaxel 75 mg/m 2 IV day 1 Carboplatin AUC 6 IV day 1 Cycled every 21 days for 6 cycles With Trastuzumab 4 mg/kg week 1 Trastuzumab 2 mg/kg for 17 weeks Trastuzumab 6 mg/kg IV every 3 weeks to complete 1 year of trastuzumab therapy # Cardiac monitoring at baseline, 3, 6, and 9 mo. 6

8 Mackay Memorial Hospital Practical Guideline In Breast Cancer: Neoadjuvant Setting 2014 V04 Locally advanced disease : T2,T3, with/without N2, fixed node Non-trastuzumab containing regimens Preferred regimen FEC/CEF followed by Docetaxel FEC Docetaxel FEC followed by Docetaxel [1] 5-Fluorouracil 500 mg/m2 IV day 1 Epirubicin mg/m2 IV day 1 Cyclophosphamide 500 mg/m2 day 1 Cycled every 21 days for 4 cycles. Docetaxel mg/m2 day 1 Cycled every 21 days for 4 cycles Others regimens AC (doxorubicin/cyclophosphamide) EC (epirubicin/cyclophosphamide) FAC/CAF (5-fluorouracil/ doxorubicin/cyclophosphamide) CMF (cyclophosphamide/methotrexate/5-fluorouracil) AC /EC/ FAC/ CAF followed by Taxanes (Docetaxel.Paclitaxel) TAC (docetaxel/ doxorubicin/cyclophosphamide) Trastuzumab containing regimens Preferred regimen FEC/CEF followed by Docetaxel/ trastuzumab FEC Docetaxel FEC followed by Docetaxel/ trastuzumab [2] 5-Fluorouracil 500 mg/m2 IV day 1 Epirubicin mg/m2 IV day 1 Cyclophosphamide 500 mg/m2 day 1 Cycled every 21 days for 4 cycles. Docetaxel mg/m2 day 1 Cycled every 21 days for 4 cycles Trastuzumab 8 mg/kg IV with first dose of docetaxel or Trastuzumab 6 mg/kg IV with Other Three dose of docetaxel Trastuzumab 6 mg/kg IV every 3 wk to complete 1 y of treatment. 7

9 Others regimens Docetaxel/ Trastuzumab followed by FEC (5-fluorouracil/ epirubicin/cyclophosphamide) T + Trastuzumab followed by FEC + Trastuzumab [3] (Paclitaxel+Trastuzumab followed by 5-fluorouracil/ doxorubicin/cyclophosphamide +Trastuzumab) 8

10 參考文獻 : 1.Weiss, R.B., et al., Adjuvant chemotherapy after conservative surgery plus irradiation versus modified radical mastectomy. Analysis of drug dosing and toxicity. Am J Med, (3): p Poole, C.J., et al., Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med, (18): p Bonadonna, G., et al., Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med, (8): p Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol, (3): p Levine, M.N., et al., Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol, (8): p Roche, H., et al., Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol, (36): p Martin, M., et al., Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer. J Natl Cancer Inst, (11): p Sparano, J.A., et al., Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med, (16): p Henderson, I.C., et al., Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol, (6): p Jones, S.E., et al., Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol, (34): p Martin, M., et al., Adjuvant docetaxel for node-positive breast cancer. N Engl J Med, (22): p Citron, M.L., et al., Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial J Clin Oncol, (8): p Romond, E.H., et al., Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, (16): p Tan-Chiu, E., et al., Assessment of cardiac dysfunction in a randomized trial comparing 9

11 doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol, (31): p Hurley, J., et al., Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol, (12): p Piccart-Gebhart, M.J., et al., Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med, (16): p Joensuu, H., et al., Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med, (8): p