乳癌化療指引 104 年 12 月第六版 99-103 年,1 st - 5 th 版 注意事項 : 本院癌症團隊基於實證醫學制定此化學治療指引 : 本院癌症團隊基於實證醫學制定此化學治療指引, 實證醫學之結論源自臨床試驗, 實證醫學之結論源自臨床試驗, 惟參與臨床試驗之研究對象多以 70 歲以下之病人為主, 故建議 70 歲以上病人接受治療時, 應依據病人實際臨床狀況進行抗癌藥物劑量之調整!
健保藥品給付限制註記說明 : (!) : 健保有條件給付該藥品, 詳參閱最新之健保給付規定 ($) : 健保尚未給付該藥品用於此癌症化療, 詳參閱最新之健保給付規定 ( 資料彙整日期 2015.09.01) Non-trastuzumab Containing Combinations Primary/adjuvant TAC chemotherapy 1 Docetaxel 75 mg/m 2 IV day 1 Doxorubicin 50 mg/ m 2 IV day 1 Cyclophosphamide 500 mg/m 2 IV day 1 Repeat every 21 days for 6 cycles. (All cycles are with G-CSF support dose) ($) Dose-dense AC followed by docetaxel chemotherapy 2 Repeat every 14 days for 4 cycles. followed by Docetaxel 75 mg/m 2 IV on D1 (All cycles are with G-CSF support dose) ($)
Dose-dense AC followed by Paclitaxel chemotherapy 2 Repeat every 14 days for 4 cycles. followed by Docetaxel 80 mg/m 2 IV on D1 (!) Repeat weekly for 12 cycles (All cycles are with G-CSF support dose) ($) AC followed by paclitaxel chemotherapy 3. Paclitaxel 80 mg/m2 by 1h IV infusion weekly for 12 wks. (!) AC followed by docetaxel chemotherapy 3 Doxorubicin 60 mg/m 2 IV on day 1. Docetaxel 75 mg/m 2 IV on day 1 (!)
TC chemotherapy 4 Docetaxel 75 mg/m 2 IV day 1 (All cycles are with filgrastim support). ($) AC/EC chemotherapy 5.6 (or Epirubicin 90 mg/m 2 IV on D1) Cyclophosphamide 600 mg/m2 IV day 1. FAC chemotherapy with/out paclitaxel 7-8 5-Fluorouracil 500 mg/m 2 IV day 1 Doxorubicin 50 mg/m 2 IV day 1 Cyclophosphamide 500 mg/m 2 IV day 1 Repeat every 21 days for 6 cycles. ± Paclitaxel 80 mg/m 2 by 1 h IV infusion weekly for 12 wks. CMF chemotherapy 9 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 Repeat every 28 days for 6 cycles.
FEC followed by docetaxel chemotherapy 10 5-Fluorouracil 500 mg/m 2 IV days 1 Epirubicin 100 mg/m 2 IV day 1 Cyclophosphamide 500 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles. Docetaxel 75-100 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles. FEC chemotherapy by weekly paclitaxel 11 5-Fluorouracil 600 mg/m 2 IV day 1 Epirubicin 90 mg/m 2 IV on D1. : Paclitaxel 100 mg/m 2 IV infusion weekly for 8 wks (! )
Reference: 1. Adjuvant Docetaxel for Node-Positive Breast Cancer. N Engl J. Med 352: 2302-2313 (2005) 2. Evaluation of anemia, neutropenia and skin toxicities in standard or dose-dense doxorubicin/cyclophosphamide (AC)-paclitaxel or docetaxel adjuvant chemotherapy in breast cancer. Ann Oncol.;16(2):247-52. (2005) 3. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med.;358(16):1663-71. (2008) 4. Extended follow-up and analysis by age of the US Oncology Adjuvant Trial 9735: Docetaxwl/cyclophophamide is associated with an overall survival benefit compared to doxorubicin/cyclophosphamide and is well tolerated in women 65 or older. San Antonio Breast Cancer Symposium. Abstract 12, 2007 (NCCN Guidelines Invasive Breast Cancer Version 2.2011) 5. Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990;8:1483-1496. 6. J Clin Oncol 2001;19:3103-3110. 7. Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol 1989;12; 123-128. 8. Assikis V, Buzdar A, Yang Y, et al: A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer 2003;97:2716-23. 9. 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.; 16:2651-2658. (1998) J Clin Oncol 2006; 24:5664-5671. 10. Sequential Adjuvant Epirubicin-Based and Docetaxel Chemotherapy for Node-Positive Breast Cancer Patients:The FNCLCC PACS 01 Trial 11. Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Paclitaxel for Early Breast Cancer J Natl Cancer Inst 2008;100: 805 814
Trastuzumab Containing Combinations Cardiac monitoring at baseline, 3, 6, and 9 mo. AC followed by T chemotherapy with Trastuzumab 1-2. Paclitaxel 80 mg/m 2 by 1h 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 year of treatment. (! ) (As an alternative, trastuzumab 8 mg/kg IV as loading dose and maintainance with 6 mg/kg IV every 3 wk may be used following the completion of paclitaxel, and given to complete 1 y of trastuzumab treatment.) AC followed by T chemotherapy with trastuzumab + pertuzumab. : Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Paclitaxel 80 mg/m 2 IV days 1, 8, and 15 (! ) Trastuzumab 6 mg/kg IV day 1 (! ) Repeat every 21 days to complete 1 y of trastuzumab therapy
Dose-dense AC followed by paclitaxel chemotherapy with trastuzumab 3-4 Repeat every 14 days for 4 cycles. Paclitaxel 175 mg/m 2 by 3h IV day 1 (! ) Repeat every 14 days for 4 cycles. (All cycles are with filgrastim support). With Trastuzumab 4 mg/kg IV with first dose of paclitaxel. (! ) Trastuzumab 2 mg/kg IV weekly to complete 1 y of treatment. (! ) (As an alternative, trastuzumab 8 mg/kg IV as loading dose and maintainance with 6 mg/kg IV every 3 wk may be used following the completion of paclitaxel, and given to complete 1 y of trastuzumab treatment.) TCH chemotherapy 5 Docetaxel 75 mg/m 2 IV day 1 (! ) Carboplatin AUC 6 IV day 1 (! ) Repeat every 21 days for 6 cycles With Trastuzumab 4 mg/kg wk 1. (! ) Trastuzumab 2 mg/kg for 17 wks. Trastuzumab 6 mg/kg IV every 3 wks to complete 1 year of trastuzumab therapy.
TCH chemotherapy + pertuzumab 6 Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Docetaxel 75 mg/m 2 IV day 1 (! ) Carboplatin AUC 6 IV day 1 (! ) Repeat every 21 days for 6 cycles : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy AC followed by docetaxel chemotherapy with trastuzumab 7-9. Docetaxel 75 mg/m 2 IV day 1 (! ) With Trastuzumab 4 mg/kg wk 1. (! ) Trastuzumab 2 mg/kg IV weekly for 11 wks. Trastuzumab 6 mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. (As an alternative, trastuzumab 8 mg/kg IV as loading dose and maintainance with 6 mg/kg IV every 3 wk may be used following the completion of docetaxel, and given to complete 1 y of trastuzumab treatment.)
AC followed by docetaxel chemotherapy with trastuzumab and pertuzumab Cyclophosphamide 600 mg/m2 IV day 1 : Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Docetaxel 75 mg/m 2 IV day 1 (! ) : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy Paclitaxel + Trastuzumab 12 Paclitaxel 80 mg/m 2 IV weekly for 12 weeks (! ) With Trastuzumab 4 mg/kg wk 1. followed by 2 mg/kg IV weekly for 11 wks. (! ) Trastuzumab 6 mg/kg IV every 21 days to complete 1 year of trastuzumab therapy. (As an alternative, trastuzumab 8 mg/kg IV as loading dose and maintainance with 6 mg/kg IV every 3 wk may be used following the completion of docetaxel, and given to complete 1 y of trastuzumab treatment.) Chemotherapy followed by trastuzumab 10-11 Approved adjuvant chemotherapy regimen for at least 4 cycles Trastuzumab 8 mg/kg IV wk 1 (! ) Trastuzumab 6 mg/kg IV every 21 days for 1 y.
Reference: 1. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med.;358(16):1663-71. (2008) 2. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer.;8(5):453-6. (2008) 3. Dang C, Fomier M, Sugarman S, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER2/neu over expressed/amplified breast cancer. J Clin Oncol. 2008;26(8):1216-1222. 4. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer.;8(5):453-6. (2008) 5. Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer. Oncologist.;13(5):515-25. (2008) 6. Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278-2284. 7. Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011;365:1273-1283. 8. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med.;358(16):1663-71. (2008) 9. Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278). Clin Breast Cancer.;8(5):453-6. (2008) 10. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet.;369(9555):29-36. (2007) 11. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med ; 353: 1673 84 (2005) 12. Tolaney S, Barry W, Dang C, et al: A phase II study of paclitaxel(t) and trastuzumab(h) (APT trial) for node-negative, HER2-positive breast cancer(bc). [abstract]. San Antonin Breast Cancer Symposium 2013; Abstract S1-04
Trastuzumab Containing Combinations Cardiac monitoring at baseline, 3, 6, and 9 mo. FEC chemotherapy followed by pertuzumab + trastuzumab + docetaxel 1 Fluorouracil 500 mg/m 2 IV day 1 Epirubicin 100 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles : Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Docetaxel 75 100 mg/m 2 IV day 1 (! ) Repeat every 21 days for 3 cycles : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy FEC chemotherapy followed by pertuzumab + trastuzumab + paclitaxel Fluorouracil 500 mg/m 2 IV day 1 Epirubicin 100 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles : Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Paclitaxel 80 mg/m 2 IV days 1, 8, and 15 (! ) Repeat every 21 days for 3 cycles, : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy
Pertuzumab + trastuzumab + docetaxel followed by FEC chemotherapy 2 Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Docetaxel 75 100 mg/m 2 IV day 1 (! ) adjuvant therapy Fluorouracil 600 mg/m 2 IV day 1 Epirubicin 90 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy Pertuzumab + trastuzumab + paclitaxel followed by FEC chemotherapy Pertuzumab 840 mg IV day 1 followed by 420 mg IV ($) Trastuzumab 8 mg/kg IV day 1 followed by 6 mg/kg IV (! ) Paclitaxel 80 mg/m 2 IV days 1, 8, and 15 (! ) adjuvant therapy Fluorouracil 600 mg/m 2 IV day 1 Epirubicin 90 mg/m 2 IV day 1 Repeat every 21 days for 3 cycles : Trastuzumab 6 mg/kg IV every 21 days to complete 1 y of trastuzumab therapy
1. Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: 2278-2284. 2. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012 Jan;13(1):25-32
Other Consider Regimens CLF 1-2 Cyclophosphamide 600 mg/m 2 IV on D1 Pegylated Liposomal Doxorubicin (LipoDox) 35-40 mg/m 2 IV on D1 (! ) 5-Fluorouracil 600 mg/m 2 IV on D1 repeat cycle every 21 days for 6 cycles. LC 3-5 Pegylated Liposomal Doxorubicin (Lipo-Dox) 35-50 mg/m 2 IV on D1 (! ) Cyclophosphamide 500-600 mg/m2 IV on D1 repeat cycle every 21-28 days for 4 cycles 1. Pegylated liposomal doxorubicin for adjuvant treatment of breast cancer in patients refusing therapy with conventional doxorubicin. Journal of Clinical Oncology, (28):suppl: 2010 ASCO Annual Meeting Proceedings e11097 (2010) 2. Pegylated liposomal doxorubicin (Lipo-Dox ) combined with cyclophosphamide and 5-fluorouracil is effective and safe as salvage chemotherapy in taxane-treated metastatic breast cancer: an open-label, multi-center, non-comparative phase II study. Rau et al. BMC Cancer (2015) 15:423 DOI 10.1186/s12885-015-1433-4 3. Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study. Ann Oncol.;22(12):2591-6. (2011) 4. Phase II trial of pegylated liposomal doxorubicin-cyclophosphamide combination as first-line chemotherapy in older metastatic breast cancer patients. Oncology.;73(3-4):210-4. (2007) 5. Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. Anticancer Res. 2014 Dec;34(12):7319-26.