Transcription

1 高雄市立小港醫院 ( 委託財團法人私立高雄醫學大學經營 ) Kaohsiung Municipal Hsiao-Kang Hospital 106 年常用化學治療處方

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3 高雄市立小港醫院 ( 委託高雄醫學大學經營 ) 常用化學處方集 目錄 乳癌 Breast Cancer... 1 肺癌 Lung Cancer 一 非小細胞肺癌 (NSCLC) 二 小細胞肺癌 (SCLC) 食道癌 Esophageal cancer 胃癌 Stomach Cancer 結腸直腸癌 Colon Cancer & Rectum Cancer 肝癌 Hepatoma 泌尿道癌 Urinary tract Cancer 一 膀胱癌 Bladder Cancer 二 前列腺癌 Prostate Cancer 淋巴癌 Hematopoietic cancer 藥物產品規格 劑量調整 常見副作用 副作用評估級數與常見處理 Alopecia( 掉髮 ) Anemia( 貧血 )

4 Anorexia ( 厭食 ) Constipation( 便秘 ) Chills rigors( 寒冷 寒顫 ) Cough( 咳嗽 ) Conjunctivitis( 結膜炎 ) Diarrhea( 腹瀉 ) Dyspepsia( 消化不良 ) Dizziness( 頭暈 ) Dyspnea( 呼吸困難 ) Fever( 發燒 ) Fluid retention( 體液滯留 ) Fatigue( 疲倦 ) Hand-foot syndrome( 手足症候群 ) Headache( 頭痛 ) Hematuria( 血尿 ) Hot flashes( 潮紅 ) Hyponatremia( 低血鈉 ) Hypocacelmia( 低血鈣 ) Hypotension( 低血壓 ) Hypokalemia( 低血鉀 )

5 Hypomagnesemia( 低血鎂 ) Insomnia( 失眠 ) Injection site reaction( 注射部位異常反應 ) Irregular menses( 月經不規則 ) Leukopenia( 白血球低下 ) LV dysfunction(lvef decreased 左心室射出率 ) Mucostitis( 口腔發炎 ) Nail disorder( 指甲變化 ) Nausea( 噁心 )/vomiting( 嘔吐 ) Neuropathy-sensory( 感覺神經病變 ) Peripheral edema( 周邊肢體水腫 ) Pruritus( 皮膚癢 ) Pain,chest( 胸痛 ) Pain,abdominal( 腹痛 ) Phlebitis( 靜脈炎 ) Rash( 紅疹 ) Renal dysfunction( 腎功能異常 ) SIADH( 抗利尿激素不適當分泌症候群 ) Sinus bradycardia( 竇性心搏過慢 ) Thrombocytopenia( 血小板低下 )

6 Tachycardia( 心搏過速 ) Weakness( 虛弱無力 ) 參考文獻

7 修訂日期 106 年 6 月 16 日 乳癌 Breast Cancer 治療方式 Adjuvant Regimen 1. FEC (every 3wks for 6cycles) 5FU: 500/600 mg/m² Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 2. FEC follow by Docetaxel (every 3wks for 6 or 8 cycles) 5FU: 500/600 mg/m² 處方內容 Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 3. FLC (every 3wks for 6cycles) 5FU: 500/600 mg/m² Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² 1

8 Regimen 4. FLC follow by Docetaxel ( every 3wks for 6 or 8 cycles ) 5FU: 600 mg/m² Lipo-Dox: 35 mg/m² Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² Regimen 5. EC (every 3wks for 6cycles) Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 6. EC + Docetaxel ( every 3wks for 6 or 8 cycles ) Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 7. LC (every 3wks for 6cycles) Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 8. LC + Docetaxel ( every 3wks for 6 or 8 cycles ) Lipo-Dox: 35 mg/m² 2

9 Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² ~~~Single Agents~~~ Regimen 1. T (every 3wks ) Taxotere: 75/100 mg/m² Regimen 2. P (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² Regimen 3. weekly P Paclitaxel: 80 mg/m² Regimen 4. N (every 3wks ) Navelbine 25~35 mg/m² Regimen 5. Eribulin (day 1,8 cycled every 3wks) Eribulin(Halaven): 1.4 mg/m² Regimen 6. X Capecitabine(Xeloda): 800~1000mg/ m² po bid 3

10 ~~~Other Combinations ~~~ Regimen 1.PG (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² Gemcitabine(Gemzar):1000 mg/m² Regimen 2. weekly P+G Paclitaxel(Genetaxyl): 80 mg/m² Gemcitabine(Gemzar): 800 mg/m² Regimen 3.TC (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 4.TG (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Gemcitabine(Gemzar): 800~1000 mg/m² Regimen 5.TCH Docetaxel (Taxotere): 60~75 mg/m² Carboplatin(Kemocarb): (Ccr+25) x AUC mg/m² Trastuzumab(Herceptin): 6mg/kg q3wk 4

11 標靶治療 1.Herceptin: loading dose 8mg/kg,maintain dose 6mg/kg,Q21d 處方內容 2.Perjeta(with Herceptin and Taxotere): loading dose 840mg,maintain dose 420mg,Q21d 3.TDM-1(Kadcyla):3.6mg/kg,Q21d 4.Avastin(with Paclitaxel) 5-10mg/kg,Q21d 5.Afinitor(Everolimus)10mg PO,QD 賀爾蒙治療 處方內容 1.Nolvadex 10mg PO,BID 2.Femara 2.5mg PO,QD 3.Exemestane (Aromasin)25mg PO,QD 治療方式 Neoadjuvant Regimen 1. FEC (every 3wks for 6cycles) 5FU: 500/600 mg/m² 處方內容 Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 2. FEC + Docetaxel ( every 3wks for 6 or 8 cycles ) 5FU: 500/600 mg/m² Epirubicin: 75/90 mg/m² 5

12 Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 3. FLC (every 3wks for 6cycles) 5FU: 500/600 mg/m² Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 4. FLC + Docetaxel ( every 3wks for 6 or 8 cycles ) 5FU: 600 mg/m² Lipo-Dox: 35 mg/m² Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² Regimen 5. EC (every 3wks for 6cycles) Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 6. EC + Docetaxel ( every 3wks for 6 or 8 cycles ) Epirubicin: 75/90 mg/m² 6

13 Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 7. LC (every 3wks for 6cycles) Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 8. LC + Docetaxel ( every 3wks for 6 or 8 cycles ) Lipo-Dox: 35 mg/m² Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² ~~~Single Agents~~~ Regimen 1. T (every 3wks ) Taxotere: 75/100 mg/m² Regimen 2. P (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² 7

14 Regimen 3. weekly P (every 3wks ) Paclitaxel: 80 mg/m² Regimen 4. N (every 3wks ) Navelbine 25~35 mg/m² Regimen 5. Eribulin (day 1,8 cycled every 3wks) Eribulin(Halaven): 1.4 mg/m² Regimen 6. X Capecitabine(Xeloda): 800~1000mg/ m² po bid ~~~Other Combinations ~~~ Regimen 1.PG (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² Gemcitabine(Gemzar):1000 mg/m² Regimen 2. weekly P+G Paclitaxel(Genetaxyl): 80 mg/m² Gemcitabine(Gemzar): 800 mg/m² 8

15 Regimen 3.TC (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 4.TG (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Gemcitabine(Gemzar): 800~1000 mg/m² Regimen 5.TCH Docetaxel (Taxotere): 60~75 mg/m² Carboplatin(Kemocarb): (Ccr+25) x AUC mg/m² Trastuzumab(Herceptin): 6mg/kg q3wk 標靶治療 1.Herceptin: loading dose 8mg/kg,maintain dose 6mg/kg,Q21d 2.Perjeta(with Herceptin and Taxotere): loading dose 840mg,maintain 處方內容 dose 420mg,Q21d 3.TDM-1(Kadcyla):3.6mg/kg,Q21d 4.Avastin(with Paclitaxel) 5-10mg/kg,Q21d 5.Afinitor(Everolimus)10mg PO,QD 9

16 賀爾蒙治療 處方內容 1.Nolvadex 10mg PO,BID 2.Femara 2.5mg PO,QD 3.Exemestane (Aromasin)25mg PO,QD 治療方式 Recurrent or Metastatic Regimen 1. FEC (every 3wks for 6cycles) 5FU: 500/600 mg/m² Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 2. FEC + Docetaxel ( every 3wks for 6 or 8 cycles ) 處方內容 5FU: 500/600 mg/m² Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 3. FLC (every 3wks for 6cycles) 5FU: 500/600 mg/m² Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² 10

17 Regimen 4. FLC + Docetaxel ( every 3wks for 6 or 8 cycles ) 5FU: 600 mg/m² Lipo-Dox: 35 mg/m² Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² Regimen 5. EC (every 3wks for 6cycles) Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 6. EC + Docetaxel ( every 3wks for 6 or 8 cycles ) Epirubicin: 75/90 mg/m² Cyclophosphamide: 500/600 mg/m² Docetaxel: 75/100 mg/m² Regimen 7. LC (every 3wks for 6cycles) Lipo-Dox: 30/35 mg/m² Cyclophosphamide: 500/600 mg/m² 11

18 Regimen 8. LC + Docetaxel ( every 3wks for 6 or 8 cycles ) Lipo-Dox: 35 mg/m² Cyclophosphamide: 600 mg/m² Docetaxel:75/100 mg/m² ~~~Single Agents~~~ Regimen 1. T (every 3wks ) Taxotere: 75/100 mg/m² Regimen 2. P (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² Regimen 3. weekly P (every 3wks ) Paclitaxel: 80 mg/m² Regimen 4. N (every 3wks ) Navelbine 25~35 mg/m² Regimen 5. Eribulin (day 1,8 cycled every 3wks) Eribulin(Halaven): 1.4 mg/m² 12

19 Regimen 6. X Capecitabine(Xeloda): 800~1000mg/ m² po bid ~~~Other Combinations ~~~ Regimen 1.PG (every 3wks ) Paclitaxel(Genetaxyl): 175 mg/m² Gemcitabine(Gemzar):1000 mg/m² Regimen 2. weekly P+G Paclitaxel(Genetaxyl): 80 mg/m² Gemcitabine(Gemzar): 800 mg/m² Regimen 3.TC (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Cyclophosphamide: 500/600 mg/m² Regimen 4.TG (every 3wks ) Docetaxel (Taxotere): 75 mg/m² Gemcitabine(Gemzar): 800~1000 mg/m² 13

20 Regimen 5.TCH Docetaxel (Taxotere): 60~75 mg/m² Carboplatin(Kemocarb): (Ccr+25) x AUC mg/m² Trastuzumab(Herceptin): 6mg/kg q3wk 標靶治療 1.Herceptin: loading dose 8mg/kg,maintain dose 6mg/kg,Q21d 處方內容 2.Perjeta(with Herceptin and Taxotere): loading dose 840mg,maintain dose 420mg,Q21d 3.TDM-1(Kadcyla):3.6mg/kg,Q21d 4.Avastin(with Paclitaxel) 5-10mg/kg,Q21d 5.Afinitor(Everolimus)10mg PO,QD 賀爾蒙治療 處方內容 1.Nolvadex 10mg PO,BID 2.Femara 2.5mg PO,QD 3.Exemestane (Aromasin)25mg PO,QD 參考文獻 1. 全民健康保險藥品給付規定 2. 高雄醫學大學附設中心紀念醫院癌症中心化學治療處方集 3. 高雄市立小港醫院 (2016).Antineoplastic agents. 處方集 4. National Comprehensive Cancer Network. (2017). NCCN Clinical Practice 14

21 Guidelines in Oncology: Breast Cancer, version Eloy, J. O., Petrilli, R., Chesca, D. L., Saggioro, F. P., Lee, R. J., & Marchetti, J. M. (2017). Anti-HER2 immunoliposomes for co-delivery of paclitaxel and rapamycin for breast cancer therapy. European Journal of Pharmaceutics and Biopharmaceutics, 115, Jones, S., Holmes, F. A., O'Shaughnessy, J., Blum, J. L., Vukelja, S. J., McIntyre, K. J.,... & Hyman, W. J. (2009). Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735.Journal of Clinical Oncology, 27(8), Martin, M., Pienkowski, T., Mackey, J., Pawlicki, M., Guastalla, J. P., Weaver, C.,... & Guevin, R. (2005). Adjuvant docetaxel for node-positive breast cancer.new England Journal of Medicine, 352(22), O brien, M. E. R., Wigler, N., Inbar, M. C. B. C. S. G., Rosso, R., Grischke, E., Santoro, A.,... & Orlandi, F. (2004). Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX /Doxil ) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Annals of oncology, 15(3), Roché, H., Fumoleau, P., Spielmann, M., Canon, J. L., Delozier, T., Serin, D.,... & Viens, P. (2006). Sequential adjuvant epirubicin-based and docetaxel 15

22 chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. Journal of Clinical Oncology, 24(36), Romond, E. H., Perez, E. A., Bryant, J., Suman, V. J., Geyer Jr, C. E., Davidson, N. E.,... & Swain, S. M. (2005). Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. New England Journal of Medicine, 353(16), Shahriari-Ahmadi, A., Arabi, M., Payandeh, M., & Sadeghi, M. (2017). The recurrence frequency of breast cancer and its prognostic factors in Iranian patients. International Journal of Applied and Basic Medical Research, 7(1), Teshome, M., & Kuerer, H. M. (2017). Breast conserving surgery and locoregional control after neoadjuvant chemotherapy. European Journal of Surgical Oncology (EJSO). 16

23 一 非小細胞肺癌 (NSCLC) 肺癌 Lung Cancer 修訂日期 106 年 5 月 19 日 治療方式 藥物種類 劑量 間隔治療時間備註 *Gemcitabine (Gemzar ) Gemcitabine (Gemzar ) 1000mg/ m2 D1,D8,D15 Q28days 4-6 cycles Gemcitabine (Gemzar ) 1000mg/ m2 D1,D8,D15 +Cisplatin 60-75mg/ m2 D1 Gemcitabine (Gemzar )1000mg/ m2 D1,D8,D15 +Carboplatin (AUC=5) D1 *Vinorelbine (Navelbine ) Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,D15 Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,or D15+Cisplatin 60-75mg/ m2 D1 Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,or D15+Carboplatin (AUC=5) D1 Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles CCr 60 CCr<60 CCr 60 CCr<60 17

24 藥物種類 劑量 間隔治療時間備註 Vinorelbine (Navelbine ) ORAL 20mg Navelbine 25mg/m2 D1 D8 *Paclitaxel (Genetaxyl ) Paclitaxel mg/ m2 D1,D8,D15 Paclitaxel mg/ m2 D1,D8,D15 +Cisplatin 60-75mg/ m2 D1 Paclitaxel mg/ m2 D1,D8,D15 +Carboplatin (AUC=5) D1 *Docetaxel (Taxotere ) Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 +Cisplatin 60-75mg/ m2 D1 Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 +Carboplatin (AUC=5) D1 Q3W 21Days 4-6cycle Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles 前三次依體表面積每週給藥 60mg/m 2 一次, 第四次開始增加每週 80mg/m 2 一次 第 Ⅱ ⅢA 期根治性手術後輔助治療 ( 配合放療 )+Cisplatin/carboplatin CCr 60 CCr<60 CCr 60 CCr<60 18

25 藥物種類 劑量 間隔治療時間備註 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 +Cisplatin 60-75mg/ m2 D1 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 +Carboplatin (AUC=5) D1 *Pemetrexed (Alimta ) Pemetrexed (Alimta ) 500mg/ m 2 D1 Pemetrexed (Alimta ) 500mg/ m 2 D1 +Cisplatin 60-75mg/ m2 D1 Pemetrexed (Alimta ) 500mg/ m 2 D1 +Carboplatin (AUC=5) D1 Gefitinib (Iressa ) 250 mg Erlotinib (Tarceva ) 150 mg Afatinib (Giotrif ) 40 mg Osimertinib(Tagrisso) 80mg Q21days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q21days 4-6 cycles Q21days 4-6 cycles Q21days 4-6 cycles QD QD QD QD CCr 60 CCr<60 CCr 60 需經健保事前審查核准後使用 CCr<60 需經健保事前審查核准後使用需經健保事前審查核准後使用需經健保事前審查核准後使用需經健保事前審查核准後使用 T790M EGFR 突變 ( 自費 ) Crizotinib(Xalkori) 250mg Bid ALK 陽性 Ceritinib(zykadia) 150mg QD( 最高劑量 750mg) 需經健保事前審查核准後使用 *UFUR mg QD or 200 mg BID Indication: Adeno, pt2 and tumor size > 3 cm 2 years 19

26 二 小細胞肺癌 (SCLC) 治療方式 Adjuvant 藥物種類 劑量 間隔 治療時間 備註 Etoposide(VP-16) 100 mg/m2 D1-D3 +Cisplatin 60-75mg/m2 D1 Etoposide(VP-16) 100 mg/m2 D1-D3 +Carboplatin (AUC=5) D1 Topotecan 1.5mg/m 2 D1-D5 參考文獻 Q21 days 6 cycles Q21 days 6 cycles Q21 days 4-6 cycles Ccr 60 Ccr<60 1.Guilbault, C., Garant, A., Faria, S., Owen, S., Ofiara, L., Duclos, M.,... & Kopek, N. (2017). Long-term outcomes of induction carboplatin and gemcitabine followed by concurrent radiotherapy with low-dose paclitaxel and gemcitabine for stage III non-small cell lung cancer. Clinical Lung Cancer. 2.Miyawaki, M., Naoki, K., Yoda, S., Nakayama, S., Satomi, R., Sato, T.,... & Namkoong, H. (2017). Erlotinib as second-or third-line treatment in elderly patients with advanced non-small cell lung cancer: Keio Lung Oncology Group Study 001 (KLOG001). Molecular and Clinical Oncology, 6(3), Palka, M., Sanchez, A., Córdoba, M., Díaz Nuevo, G., Varela De Ugarte, A., 20

27 Cantos, B.,... & Provencio, M. (2017). Cisplatin plus vinorelbine as induction treatment in stage IIIA non-small cell lung cancer. Oncology Letters, 13(3), Pirker, R. (2017). Milestones in the systemic treatment of lung cancer. memo-magazine of European Medical Oncology, 10(1),

28 修訂日期 106 年 4 月 18 日 食道癌 Esophageal cancer 治療方式 Adjuvant 1 st line : C/T alone High dose [5-FU 2000 mg/m 2 + LV 150 mg/m 2 + N/S 250ml keep 24 hrs] Q1Week +[ Cisplatin 30 mg/m 2 + N/S 500ml keep 2hrs] Q1Week (if CCr < 60 ml/min, Cisplatin 改為 [Carboplatin ((CCr+25)x3~5mg) + N/S 500ml keep 2hrs] Q3Week ) Low dose 處方內容 [5-FU (200mg/m 2 /day x1~5days) + N/S 250ml keep1~5days + Bloodlet(Calcium folinate15mg) 2# PO Bid 1~5days] Q1Week +[Cisplatin 25mg/m 2 + N/S 500ml keep 2hrs] Q1Week (if CCr < 60 ml/min, Cisplatin 改為 [Carboplatin ((CCr+25)x3~5mg) + N/S 500ml keep 2hrs] Q3Week ) Taxane-based Taxotere (75 mg/m 2 ) + N/S 500ml keep 2hrs Q3Week Paclitaxol (60~100mg/m 2 ) + N/S 500ml keep 2hrs Q1Week Combined with Platium/5FU 22

29 [Taxotere ( 40 mg/m 2 ) + N/S 250ml keep 2hrs ] + [Cisplatin (30 mg/m 2 ) + N/S 500ml keep 2hrs ] + [5-FU (2000 mg/m 2 ) + LV 150 mg/ m 2 + N/S 250mlkeep 24hrs ] Q2Week [Paclitaxol(70 mg/m 2 ) + N/S 250ml keep 2hrs ] + [Cisplatin (30 mg/m 2 ) + N/S 500ml keep 2hrs ] + [5-FU (2000 mg/m 2 ) + LV 150 mg/ m 2 + N/S 250ml keep 24hrs ] Q2Week (if CCr < 60 ml/min, Cisplatin 改為 [Carboplatin ((CCr+25)x2~3mg) + N/S 250ml keep 2hrs] Q2Week ) Single Irinotecan Irinotecan (Campto) (150~180mg/ m 2 ) + N/S 250ml keep 2hrs Q2week Combine Platium [ Irinotecan (Campto) (150~180mg/m 2 ) + N/S 250ml keep 2hrs] + [Cisplatin(30 mg/m 2 ) + N/S 500ml keep 2hrs] Q2week (if CCr < 60 ml/min, Cisplatin 改為 [Carboplatin ((CCr+25)x2~3mg) + N/S 250ml keep 2hrs] Q2Week ) 23

30 參考文獻 1. van Ruler, M. A., Peters, F. P., Slingerland, M., Fiocco, M., Grootenboers, D. A., Vulink, A. J.,... & Neelis, K. J. (2017). Clinical outcomes of definitive chemoradiotherapy using carboplatin and paclitaxel in esophageal cancer. Diseases of the esophagus: official journal of the International Society for Diseases of the Esophagus, 30(4), Xia, Y., Li, Y. H., Chen, Y., Zhang, J. H., Liu, Q., Deng, J. Y.,... & Badakhshi, H. (2017). A phase II study of concurrent chemoradiotherapy combined with a weekly paclitaxel and 5-fluorouracil regimen to treat patients with advanced oesophageal carcinoma. Radiation Oncology, 12(1), Zhao, C., Lin, L., Liu, J., Liu, R., Chen, Y., Ge, F.,... & Xu, J. (2016). A phase II study of concurrent chemoradiotherapy and erlotinib for inoperable esophageal squamous cell carcinoma. Oncotarget, 7(35),

31 修訂日期 106 年 6 月 16 日 胃癌 Stomach Cancer High risk group : With lymph node(+) or T3(+)or ECOG performance status 0-2 Neo-adjuvant chemotherapy 1. TS-1 ± R/T: TS mg PO BID x 14 days, 7 days off Cycled every 6 weeks TS mg PO BID x 28 days, 14 days off Cycled every 6 weeks 2. Xeloda ± R/T: Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks 3. UFUR ± R/T : Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 4. XELOX ± R/T : Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks 25

32 5. FOLFOX4 ± R/T: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 Adjuvant chemotherapy 1. FOLFOX4: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 2. XELOX: Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off 3. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 26

33 Metastatic/Locally Advanced/Recurrent chemotherapy 1. FOLFOX4: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 2. XELOX: Oxaliplatin 130 mg/m 2 in 5%G/w 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off 3. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 4. TS-1: TS mg PO BID x 28 days, 14 days off Cycled every 6 weeks TS mg PO BID x 14 days, 7 days off Cycled every 6 weeks 5. DCF: Docetaxel 75 mg/m 2 in N/S 250ml IVD 90mins Day1 Cisplatin 75 mg/m 2 in N/S 500ml IVD 4hrs Day1 5-FU 750mg/m 2 in N/S 500ml IVD 24hrs on Day 1-5 Q3 weeks x8 cycles 27

34 6. ECF: Epirubicin 50mg/m2 in N/S 250ml IVD 2hrs Cisplatin 60 mg/m 2 in N/S 500ml IVD 4hrs 5-FU 200mg/m 2 in N/S 500ml IVD 24hrs on Days 1-21 Cycled every 21 days 7. ECF modification: Epirubicin 50mg/m2 in N/S 250ml IVD 2hrs Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. 5-FU 200mg/m 2 in N/S 500ml IVD 24hrs on Days 1-21 Cycled every 21 days 8. ECX: Epirubicin 50mg/m2 in N/S 250ml IVD 2hrs on Day 1 Cisplatin 60 mg/m 2 in N/S 500ml IVD 4hrs Day 1 Capecitabine 625 mg/m 2 PO BID Day 1-21 Cycled every 21 days 9. EOX: Epirubicin 50mg/m2 in N/S 250ml IVD 2hrs on Day 1 Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Capecitabine 625 mg/m 2 PO BID Day 1-21 Cycled every 21 days 28

35 10. FLO: Oxaliplatin 85 mg/m 2 in 5%G/w 250 ml IVD 2hrs on Day 1 Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 5-FU 2600mg/m 2 in N/S 1000ml IVD 24hrs on Day 1 Cycled every 14 days 11. Taxane: Docetaxel mg/m 2 in N/S 250ml IVD 1hr Cycled every 21 days Paclitaxel mg/m 2 in N/S 250ml IVD 1hr Cycled every 21 days Paclitaxel 80 mg/m 2 in N/S 250ml IVD 1hr weekly Cycled every 28 days Paclitaxel 80 mg/m 2 in N/S 250ml IVD 1hr on Days 1, 8, and 15 Cycled every 28 days 12. Irinotecan: Irinotecan mg/m2 IV on Day 1 Cycled every 21 days Irinotecan mg/m2 IV on Day 1 Cycled every 14 days Irinotecan 125 mg/m2 IV on Days 1 and 8 Cycled every 21 days 13. FOLFIRI: Irinotecan 180 mg/m 2 IV in N/S 500 ml IVD 2hrs Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs (Irinotecan 和 Leucovorin 同時滴 ) 29

36 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks 14. Ramucirumab: Ramucirumab 8 mg/kg IVD in N/S 250ml IVD 1hr Cycled every 14 days 15. Ramucirumab and Paclitaxel: Ramucirumab 8 mg/kg IVD in N/S 250ml IVD 1hr on Days 1 and 15 Paclitaxel 80 mg/m 2 in N/S 250ml IVD 1hr on Days 1, 8, and 15 Cycled every 28 days 16. Trastuzumab(with chemotherapy): HER2: IHC 3+or IHC 2+ and FISH(+) Trastuzumab is not recommended for use with anthracyclines Trastuzumab 8mg/kg IV loading dose on Day 1 of cycle 1, then Trastuzumab 6mg/kg IV every 21 days Trastuzumab 6mg/kg IV loading dose on Day 1 of cycle 1, then Trastuzumab 4mg/kg IV every 14 days 30

37 參考文獻 1. Ychou, M., Boige, V., Pignon, J. P., Conroy, T., Bouché, O., Lebreton, G.,... & Genève, J. (2011). Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. Journal of Clinical Oncology, 29(13), Guimbaud, R., Louvet, C., Ries, P., Ychou, M., Maillard, E., André, T.,... & Etienne, P. L. (2014). Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. Journal of Clinical Oncology, 32(31), Sasako, M., Sakuramoto, S., Katai, H., Kinoshita, T., Furukawa, H., Yamaguchi, T.,... & Ohashi, Y. (2011). Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. Journal of Clinical Oncology, 29(33), Van Cutsem, E., Sagaert, X., Topal, B., Haustermans, K., & Prenen, H. (2016). Gastric cancer. The Lancet, 388(10060), Mihmanli, M., Ilhan, E., Idiz, U. O., Alemdar, A., & Demir, U. (2016). Recent 31

38 developments and innovations in gastric cancer. World journal of gastroenterology, 22(17), Digklia, A., & Wagner, A. D. (2016). Advanced gastric cancer: Current treatment landscape and future perspectives. World journal of gastroenterology, 22(8),

39 修訂日期 106 年 6 月 16 日結腸直腸癌 Colon Cancer & Rectum Cancer Neo-adjuvant chemotherapy (T3 or N+ in rectal cancer or T4 in colon cancer) 1. FOLFOX4 ± R/T: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 2. XELOX ± R/T: Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off 3. Xeloda ± R/T: Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks 4. UFUR ± R/T: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 33

40 5. mfolfox6± R/T: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs(Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Adjuvant chemotherapy ( T3, N0, M0, Stage II No high-risk feature) 1. 5-FU/leucovorin-5-FU/LV (slv5fu2) Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks. 2. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 3. Xeloda: Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks (stage II 需自費 ) 34

41 ( T3, N0, M0, Stage II At high-risk feature for systemic recurrence or T4, N0, M0) 1. 5-FU/leucovorin-5-FU/LV (slv5fu2) Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks. 2. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 3. Xeloda:(stage II 需自費 ) Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks 4. FOLFOX4:(stage II 需自費 ) Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 35

42 5. mfolfox6:(stage II 需自費 ) Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs(Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs 6. XELOX:(stage II 需自費 ) Oxaliplatin 130 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off (T any, N1-2, M0, Stage III) 1. FOLFOX4: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 36

43 2. mfolfox6: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs 3. Xeloda: Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks (stage II 需自費 ) 4. 5-FU/leucovorin-5-FU/LV (slv5fu2) Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks. 5. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. 37

44 (T any, N any, M1, Stage IV Metastatic/Recurrent chemotherapy) 1. FOLFOX4 Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 200mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs on Day 1 and Day 2 5-FU 600mg/m 2 in N/S 500ml IVD 22hrs on Day 1 and Day 2 2. FOLFOX6: Oxaliplatin 85 mg/m 2 in 5%G/W 250 ml IVD 2hrs. Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs (Oxaliplatin 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs 3. FOLFIRI Irinotecan 180 mg/m 2 IV in N/S 500 ml IVD 2hrs Leucovorin 400mg/m 2 in N/S 250ml IVD 2hrs (Irinotecan 和 Leucovorin 同時滴 ) 5-FU 400mg/m 2 in N/S 250ml IVD 2hrs 5-FU 2400mg/m 2 in N/S 500ml IVD keep 46hrs Repeat every 2 weeks 38

45 4. XELOX Oxaliplatin 85 mg/m 2 in 5%G/w 250 ml IVD 2hrs. Capecitabine mg/m 2 PO BID x 14 days, 7 days off 5. Xeloda: Capecitabine mg/m 2 PO BID x 14 days, 7 days off Cycled every 3 weeks 6. UFUR: Tegafur 200 mg PO BID. Tegafur 100 mg PO TID. (With Target therapy) 1. FOLFIRI + bevacizumab Bevacizumab 5 mg/kg IV, day 1 Repeat every 2 weeks 2. FOLFIRI + cetuximab (KRAS/NRAS WT only) Cetuximab 400 mg/m2 IV over 2 hours first infusion, then 250 mg/m2 IV over 60 minutes weekly or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks 39

46 3. FOLFIRI + ziv-aflibercept Ziv-aflibercept 4 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks 4. FOLFOX + panitumumab (KRAS/NRAS WT only) Panitumumab 6 mg/kg IV over 60 minutes, day 1 Repeat every 2 weeks 5. FOLFOX + bevacizumab Bevacizumab 5 mg/kg IV, day 1 Repeat every 2 weeks 6. Cetuximab (KRAS/NRAS WT only) Cetuximab 400 mg/m2 first infusion, then 250 mg/m2 IV weekly or Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks 7. Panitumumab26 (KRAS/NRAS WT only) Panitumumab 6 mg/kg IV over 60 minutes every 2 weeks 8. Regorafenib Regorafenib 160 mg PO daily days 1 21 Repeat every 28 days 40

47 參考文獻 1.Lenz, H., Niedzwiecki, D., Innocenti, F., Blanke, C., Mahony, M. R., O'Neil, B. H.,... & Goldberg, R. (2014). 501ocalgb/Swog 80405: phase III trial of irinotecan/5-fu/leucovorin (folfiri) or oxaliplatin/5-fu/leucovorin (mfolfox6) with bevacizumab (bv) or cetuximab (cet) for patients (pts) with expanded Ras analyses untreated metastatic adenocarcinoma of the colon or rectum (mcrc). Annals of Oncology, 25(suppl 4), mdu Heinemann, V., von Weikersthal, L. F., Decker, T., Kiani, A., Vehling-Kaiser, U., Al-Batran, S. E.,... & Kullmann, F. (2014). FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. The lancet oncology, 15(10), Van Cutsem, E., Tabernero, J., Lakomy, R., Prenen, H., Prausová, J., Macarulla, T.,... & McKendrick, J. (2012). Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. Journal of Clinical Oncology, 30(28), of metastatic colorectal cancer. Journal of clinical oncology, 21(5), Grothey, A., Van Cutsem, E., Sobrero, A., Siena, S., Falcone, A., Ychou, M.,... & Adenis, A. (2013). Regorafenib monotherapy for previously treated 41

48 metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. The Lancet, 381(9863), Douillard, J. Y., Siena, S., Cassidy, J., Tabernero, J., Burkes, R., Barugel, M.,... & Rivera, F. (2010). Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. Journal of clinical oncology, 28(31), Lin, C. Y., Chen, J. B., Chiang, F. F., Wang, H. M., Chao, T. H., Chen, C. C., & Ma, H. F. (2016). Difference between Complete Oxaliplatin Based Adjuvant Chemotherapy and Incomplete Course in Stage III Colorectal Cancer Patients in Taiwan. 中華民國大腸直腸外科醫學會雜誌, 27(2), Gustavsson, B., Carlsson, G., Machover, D., Petrelli, N., Roth, A., Schmoll, H. J.,... & Gibson, F. (2015). A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clinical colorectal cancer, 14(1), Karoui, M., Rullier, A., Luciani, A., Bonnetain, F., Auriault, M. L., Sarran, A.,... & Sobhani, I. (2015). Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon 42

49 cancers: a multicentre randomised controlled phase II trial the PRODIGE 22-ECKINOXE trial. BMC cancer, 15(1), Lonardi, S., Sobrero, A., Rosati, G., Di Bartolomeo, M., Ronzoni, M., Aprile, G.,... & Marchetti, P. (2016). Phase III trial comparing 3 6 months of adjuvant FOLFOX4/XELOX in stage II III colon cancer: safety and compliance in the TOSCA trial. Annals of Oncology, 27(11),

50 修訂日期 106 年 5 月 9 日 治療方式 處方內容 肝癌 Hepatoma Target therapy(adjuvant) (1) Nexavar(sorafenib) 1# - 2#/day q12h 治療方式 處方內容 Systemic Oral Chemotherapy (1) UFUR 1# - 2#/day q12h 治療方式 Chemotherapy drugs: maybe used single or in combination 處方內容 (Palliative) TACE (1)Epirubicin (10-30mg)/m 2 (2)Mitomycin C(2~10mg)/m 2 (3)Cisplatin(2-40mg)/m 2 Target therapy(palliative) (1) Nexavar(sorafenib) 1# - 2#/day q12h 參考文獻 1. 高雄醫學大學附設中心紀念醫院癌症中心化學治療處方集 2. Kim, J. H., Sinn, D. H., Shin, S. W., Cho, S. K., Kang, W., Gwak, G. Y.,... & Choi, M. S. (2017). The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE. Clinical 44

51 and Molecular Hepatology, 23(1), National Comprehensive Cancer Network. (2016). NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers, version Siddique, O., Yoo, E. R., Perumpail, R. B., Perumpail, B. J., Liu, A., Cholankeril, G., & Ahmed, A. (2017). The importance of a multidisciplinary approach to hepatocellular carcinoma. Journal of Multidisciplinary Healthcare,10, Zhu, Y. J., Zheng, B., Wang, H. Y., & Chen, L. (2017). New knowledge of the mechanisms of sorafenib resistance in liver cancer. Acta Pharmacologica Sinica. 45

52 修訂日期 106 年 5 月 9 日泌尿道癌 Urinary tract Cancer 一 膀胱癌 Bladder Cancer 治療方法 Neoadjuvant Systemic Regimen1:(Ccr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) Gemcitabine (Gemzar ) 1000mg/ m2 D1, D8, D15;Cisplatin 70mg/m 2 D2 處方內容 Repeat every 28days for 3-4 cycles. Regimen2: (Ccr<50) Gemcitabine (Gemzar )1000mg/m 2 300mg/m 2 D2 Repeat every 28days for 3-4 cycles. D1, D8, D15 ; Carboplatin Regimen3: ( C Cr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Cisplatin 46

53 70mg/m 2 Regimen4: (Ccr<50) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Carboplatin 300mg/m 2 47

54 Adjuvant Systemic Regimen1:(Ccr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) Gemcitabine (Gemzar ) 1000mg/ m2 D1, D8, D15;Cisplatin 70mg/m 2 D2 Repeat every 28days for 3-4 cycles. 處方內容 Regimen2: (Ccr<50) Gemcitabine (Gemzar )1000mg/m 2 300mg/m 2 D2 Repeat every 28days for 3-4 cycles. D1, D8, D15 ; Carboplatin Regimen3: ( C Cr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Cisplatin 70mg/m 2 Regimen4: (Ccr<50) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Carboplatin 300mg/m 2 48

55 Intravesical (IC) Regimen1: Epirubicin 30-50mg qw*6-8cycles Regimen2: Mitomycin 30mg qw*6-8cycles Regimen3: Mitomycin 30mg *1cycles Epirubicin(Pharmorubicin ) 30-50mg *1cycles Within 24 hrs after resection single use Metastatic Chemotherapy drug for Urothelial cell carcinoma As Neo-adjuvant or Adjuvant regiment 參考文獻 1. 高雄醫學大學附設中心紀念醫院癌症中心化學治療處方集 2. 高雄市立小港醫院 (2016).Antineoplastic agents. 處方集 3. National Comprehensive Cancer Network. (2010). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer V. 1,

56 4.von der Maase, H., Sengelov, L., Roberts, J. T., Ricci, S., Dogliotti, L., Oliver, T.,... & Arning, M. (2005). Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. Journal of Clinical Oncology, 23(21), Roberts, J. T., von der Maase, H., Sengeløv, L., Conte, P. F., Dogliotti, L., Oliver, T.,... & Arning, M. (2006). Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer. Annals of oncology, 17(suppl 5), v118-v Chang, S. S., Bochner, B. H., Chou, R., Dreicer, R., Kamat, A. M., Lerner, S. P.,... & Quale, D. Z. (2017). Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. The Journal of Urology. 7. Ho, P. L., Willis, D. L., Patil, J., Xiao, L., Williams, S. B., Melquist, J. J.,... & Navai, N. (2016, February). Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: The MD Anderson Cancer Center Experience. In Urologic Oncology: Seminars and Original Investigations (Vol. 34, No. 2, 50

57 pp. 59-e1). Elsevier. 8. Ho, P. L., Willis, D. L., Patil, J., Xiao, L., Williams, S. B., Melquist, J. J.,... & Navai, N. (2016, February). Outcome of patients with clinically node-positive bladder cancer undergoing consolidative surgery after preoperative chemotherapy: The MD Anderson Cancer Center Experience. In Urologic Oncology: Seminars and Original Investigations (Vol. 34, No. 2, pp. 59-e1). Elsevier. 51

58 二 前列腺癌 Prostate Cancer 修訂日期 106 年 5 月 19 日 CRPC Case 適用 (castration resistance prostate cancer) Systemic Regimen1: 處方內容 Docetaxel (Taxotere ) 75mg/m 2 + Prednisolone 1# bid 5days/ 21~ Q28d,6~8 course 參考文獻 1.Papandreou, C. N., Daliani, D. D., Thall, P. F., Tu, S. M., Wang, X., Reyes, A.,... & Logothetis, C. J. (2002). Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate. Journal of clinical oncology, 20(14), Noda, K., Nishiwaki, Y., Kawahara, M., Negoro, S., Sugiura, T., Yokoyama, A.,... & Yamamoto, S. (2002). Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. New England Journal of Medicine, 346(2), Machiels, J. P., Mazzeo, F., Clausse, M., Filleul, B., Marcelis, L., Honhon, B.,... & Verhoeven, D. (2008). Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic 52

59 hormone-refractory prostate cancer. Journal of clinical oncology, 26(32), Osanto, S., & Luelmo, S. A. C. (2017). Chemotherapy and Androgen Receptor-Directed Treatment of Castration Resistant Metastatic Prostate Cancer. In Management of Prostate Cancer (pp ). Springer International Publishing. 5.de Morrée, E. S., Vogelzang, N. J., Petrylak, D. P., Budnik, N., Wiechno, P. J., Sternberg, C. N.,... & Choudhury, A. (2017). Association of Survival Benefit With Docetaxel in Prostate Cancer and Total Number of Cycles Administered: A Post Hoc Analysis of the Mainsail Study. JAMA oncology, 3(1), Osanto, S., & Luelmo, S. A. C. (2017). Chemotherapy and Androgen Receptor-Directed Treatment of Castration Resistant Metastatic Prostate Cancer. In Management of Prostate Cancer (pp ). Springer International Publishing. 53

60 R-CHOP 1 化療藥物名稱標準劑量單位稀釋液滴注時間 Mabthera 375 mg/m2 Cyclophosphamide 750 mg/m2 Doxorubicin 50 mg/m2 Vincristine 淋巴癌 Hematopoietic cancer 1.4 (max 2mg) 制定日期 106 年 5 月 9 日 mg/m2 N/S 500ml N/S 500ml N/S 500ml N/S 50ml Prednisolone 40 mg - keep IV pump >6hrs (D1) 2hrs (D2) 2hrs(D2) 30min (D2) TID (D2-D6) 週期 21 days Cyclophosphamide 750 mg/m2 N/S 500ml 2hrs(D1) CHOP 2 R-COP 3 COP 3 R-EPOCH 4 5 Doxorubicin 50 mg/m2 Vincristine 1.4 (max 2mg) mg/m2 Prednisolone 40 mg - Mabthera 375 mg/m2 Cyclophosphamide 750 mg/m2 Vincristine 1.4 (max 2mg) mg/m2 54 N/S 500ml N/S 50ml N/S 500ml N/S 500ml N/S 50ml Prednisolone 40 mg - N/S 500ml N/S 50ml Cyclophosphamide 750 mg/m2 Vincristine 1.4 (max 2mg) mg/m2 Prednisolone 40 mg - Mabthera 375 mg/m2 N/S 500ml Etoposide 50 mg/m2 N/S 500ml Epirubicin 10 mg/m2 N/S 500ml Vincristine 0.5 mg day N/S 500ml 2hrs(D1) 30min (D1) TID (D1-D5) keep IV pump >6hrs (D1) 2hrs(D2) 30min(D 2) TID (D2-D6) 2hrs(D1) 30min (D1) TID (D1-D5) keep IV pump >6hrs (D1) 24hrs (D2-D5) 24hrs (D2-D5) 24hrs (D2-D5) Cyclophosphamide 750 mg/m2 N/S 500ml 2hrs(D7) 21 days 21 days 21 days 21 days

61 EPOCH 4 5 R-ESHAP 6 ESHAP 7 R-ICE 8 Prednisolone 60 mg - Etoposide 50 mg/m2 N/S 500ml Epirubicin 10 mg/m2 N/S 500ml Vincristine 0.5 mg day N/S 500ml TID(D2- D7) 24hrs (D1-D4) 24hrs (D1-D4) 24hrs (D1-D4) Cyclophosphamide 750 mg/m2 N/S 500ml 2hrs(D6) Prednisolone 60 TID mg - (D1-D6) keep IV pump Mabthera 375 mg/m2 N/S 500ml >6hrs (D1) Solu-medrol 500 mg total N/S 100ml Etoposide 40 mg/m2 N/S 500ml Cisplatin 25 mg/m2 N/S 500ml 21 days 21 1hr (D2-D5) days 3hrs (D2-D5) 3hrs (D2-D5) 21 Ara-C 2000 mg/m2 N/S 500ml 2hrs(D6) Solu-medrol 500 mg total N/S 100ml Etoposide 40 mg/m2 N/S 500ml Cisplatin 25 mg/m2 N/S 500ml 1hr (D1-D4) 3hrs (D1-D4) 3hrs (D1-D4) Ara-C 2000 mg/m2 N/S 500ml 2hrs(D5) Mabthera 375 mg/m2 N/S 500ml Ifosfamide 1330 mg/m2 N/S 500ml Cisplatin or Carboplatin 25 AUC=5 mg/m2 N/S 500ml keep IV pump >6hrs(D1) 24hrs (D2-D4) +Mesna (D2-D4) 2hrs(D2-D4) 2hrs (D2) days 21 days 21 days Etoposide 100 mg/m2 N/S 500ml 2hrs(D2-D4) ICE 9 Ifosfamide 1330 mg/m2 N/S 500ml 55 24hrs (D1-D3) +Mesna 21 days

62 (D1-D3) Cisplatin or Carboplatin 25 mg/m2 N/S 500ml 2hrs(D1-D3) AUC=5 2hrs (D1) Etoposide 100 mg/m2 N/S 500ml 2hrs(D1-D3) FOR HL Epirubicin 25 mg/m2 N/S 250ml 1hrs(D1) ABVD 10 Bleomycin 10 mg/m2 N/S 250ml 1hrs(D1) 14 days Vinblastine 6 mg/m2 N/S 250ml 1hrs(D1) 參考文獻 Dacarbazine 375 mg/m2 1. 高雄市立大同醫院癌症中心化學治療處方集 N/S 250ml 1hrs(D1) 2.Czuczman, M. S., Weaver, R., Alkuzweny, B., Berlfein, J., & Grillo-López, A. J. (2004). Prolonged clinical and molecular remission in patients with low-grade or follicular non-hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. Journal of clinical oncology, 22(23),

63 3.Dunleavy, K., Pittaluga, S., Maeda, L. S., Advani, R., Chen, C. C., Hessler, J.,... & Staudt, L. M. (2013). Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. New England Journal of Medicine, 368(15), Eich, H. T., Diehl, V., Görgen, H., Pabst, T., Markova, J., Debus, J.,... & Wiegel, T. (2010). Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. Journal of Clinical Oncology, 28(27), Jermann, M., Jost, L. M., Taverna, C. H., Jacky, E., Honegger, H. P., Betticher, D. C.,... & Stahel, R. A. (2004). Rituximab EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Annals of Oncology, 15(3), Marcus, R., Imrie, K., Solal-Celigny, P., Catalano, J. V., Dmoszynska, A., Raposo, J. C.,... & Wassner-Fritsch, E. (2008). Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. Journal of Clinical Oncology, 26(28), Martín, A., Conde, E., Arnan, M., Canales, M. A., Deben, G., Sancho, J. M.,... & Nistal, S. (2008). R-ESHAP as salvage therapy for patients with relapsed 57

64 or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica, 93(12), Kewalramani T, Zelenetz AD, Nimer SD, et al. Rituximab and ICE (RICE) as second-line therapy prior to autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2004;103: Zelenetz AD, Hamlin P, Kewalramani T, et al. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-hodgkin's lymphoma. Ann Oncol 2003;14[suppl 1]:i Savage KJ, Skinnider B, Al-Mansour M, et al. Treating limited stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood 2011;118:

65 藥物產品規格 商品名 學名 劑量 5FU 5-Fluorouracil 1g/20 ml/vial Alimta Pemetrexed 100mg/Vial 500mg/Vial Avastin Bevacizumab 100mg/ 4mL/ Vial Campto Irinotecan 100mg/5ml/Vial Cisplatin Cisplatin 50mg/ 100ml/Bot Cyramza Ramucirumab 500mg/50mL/Vial Eloxatin Oxaliplatin 50 mg/10ml/vial Emthexate Methotrexate (M.T.X) 500mg/5ml/amp Erbitux Cetuximab 100mg/20ml/vial Endoxan Cyclophosphamide 500mg/vial Fytosid Etoposide(VP-16) 100mg/5ml/ Vial Gemzar Gemcitabine 200mg/Vial Genataxyl Paclitaxel 30mg/5ml/Vial Herceptin Trastuzumab 440mg/Vial Halaven Eribulin 1 mg /vial Kemocarb Carboplatin 150mg/15ml/Vial Kadcyla(TDM-1) Trastuzumab Emtansine 100mg/vial 160mg/vial Lipo-Dox Liposomal Doxorubicin 20mg/10mL/Vial Mitomycin Mitomycin C (M.M.C.) 10mg/Vial Navelbine Vinorelbine tartrate 50mg/5ml/Vial Pharmorubicin Epirubicin 10mg/Vial 50mg/Vial Perjeta Pertuzumab 420mg/vial Taxotere Taxotere 20mg/0.5ml/Vial 80mg/2ml/Vial Zaltrap Aflibercept 100mg/4mL/Vial 59

66 口服 Endoxan Cyclophosphamide 50mg/Tab Giotrif Afatinib 30 mg, 40 mg/tab Iressa Gefitinib 250 mg/tab TS1 Tegafur+Oteracil+Gimeracil 20mg/Cap Tarceva Erlotinib 150 mg/tab Tykerb Lapatinib 250 mg/tab UFUR Tegafur/ uracil 100mg/224mg/Cap Xeloda Capecitabine 500mg/Tab 60

67 劑量調整 5-Fluorouracil (5-FU) 5-Fluorouracil 老年人 : 參考成人劑量 肝臟功能異常 : 美國食品和藥物管理局核准的劑量不包含特殊的劑量調整指引, 但指出, 必須極其小心使用於肝臟損傷的患者 下面的指引也被作為參考 : Floyd(2006): 膽紅素 >5 mg/dl 避免使用 Koren(1992): 肝臟損傷 ( 程度未明確說明 ): 先給予 <50% 的劑量, 如果毒性未發生可增加劑量 腎臟功能異常 : 美國食品和藥物管理局核准的劑量不包含特殊的劑量調整指導方針, 但指出, 必須極其小心使用於腎臟損傷的患者 血液透析 :Aronoff (2007): 建議 Clcr<50 ml/minute 的成年患者不需要調整劑量, 已接受血液透析的患者僅應該給予 50% 的劑量 Kemoplat Cisplatin 老年人 : 參考成人劑量 肝臟功能異常 : 無相關資料 腎臟功能異常 : 依據廠商建議腎功能不佳者不建議給藥. 直到腎功能回復至 serum creatinine 小於 1.5mg/dl 或 BUN 小於 25mg/dl 才可以再給藥. FDA 並無提供 61

68 腎功能不佳的建議劑量 下列治療指引為專家的臨床治療建議劑量 :.Aronoff, 2007 Cl cr (ml/min) 劑量 血液透析 : 血液透析會清除部分劑量 75 % < 10 給予正常劑量的 50 % 已接受血液透析患者血液透析後給予正常劑量的 50 % 膜腹透析 (CAPD) 患者給予正常劑量的 50 % 連續性腎替代治療 (CRRT) 患者 給予正常劑量的 75 % 血液學異常 : 嗜中性白血球減少症和 / 或血小板減少症 : 1.febrile neutropenia 或長期性嗜中性白血球減少症或是中性白血球減少症引起的感染症且使用 (G-CSF) 治療的病患,cisplatin 合併 docetaxel 治療時需降低 docetaxe 的劑量由 75mg mg/m 2 調降至 60mg/m 2 2. 伴隨有嗜中性白血球降低引起的併發症發生時,cisplatin 合併 docetaxel 治療, 需降低 docetaxe 的劑量由 60mg mg/m 2 調降至 45mg/m 2 3.grade 4 的血小板低下症,cisplatin 合併 docetaxel 治療時, 需降低 docetaxe 的劑量由 75mg mg/m 2 調降至 60mg/m 2 4. 停用 docetaxel, 直到中性粒細胞 >1500 cells/cubic millmeter (mm 3 ) 和血小板 62

69 >100000cell/mm 3 5. 若毒性再度發生則須停用 docetaxel 腎功能異常是此藥劑量限制毒性 Alimta Pemetrexed 肝臟功能異常 : 3 級 ( 倍 ULN) 或 4 級 (>20 倍 ULN) 轉胺酶上升 : 減少 pemetrexed 75% 的劑量 腎臟功能異常 : CCr 45 <80ml/minute 同時有使用 NSAID: 要小心使用 CCr 45 ml/minute: 不需調整劑量 CCr< 45 ml/minute: 無劑量調整之研究證據, 廠商建議停用 毒性劑量的調整 : 血液學毒性 : Nadir ANC <500/mm 3 及 nadir platelet 50000/mm 3 : 減少 pemetrexed 75% 的劑量 Nadir platelet 50000/mm 3 沒有出血 : 減少 pemetrexed 75% 的劑量 Nadir platelet < 50000/mm 3 有出血 : 減少 pemetrexed 50% 的劑量 非血液學毒性 3 級 ( 不包括神經毒性 ): 停止治療直到恢復正常 ; 再開始治療如下 : 3 或 4 級毒性 ( 不包括黏膜炎 ): 減少 pemetrexed 75% 的劑量 63

70 3 或 4 級腹瀉或任何需要住院的腹瀉 : 減少 pemetrexed 75% 的劑量 3 或 4 級黏膜炎 : 減少 pemetrexed 50% 的劑量 ( 維持原 cisplatin 的量 ) 神經毒性 : 0-1 級 : 維持原 pemetrexed 的劑量 ( 及 cisplatin) 2 級 : 維持原 pemetrexed 的劑量, 減少 cisplatin 50% 的劑量 Avastin Bevacizumab 老年人 : 參考成人劑量 肝臟功能異常 : 目前尚無 Avastin 用在肝功能障礙的患者的安全性及療效性 腎臟功能異常 : 目前尚無 Avastin 用在肝功能障礙的患者的安全性及療效性 其他 : 1. 使用 Avastin 治療的病人有較高出血的危險性, 特別是與腫瘤相關的出血 在 Avastin 治療期間出現 3 級或 4 級出血的患者應永久停用 Avastin 2. 患者在使用 Avastin 時, 發生胃腸穿孔的危險性較高 發生胃腸穿孔的患者應永久停用 Avastin 3. 以 Avastin 治療之患者的高血壓發生率較高 臨床安全性數據顯示, 高血壓發生率可能與劑量有關 在開始給予 Avastin 治療前, 應適當控制已存在之高血壓 若發生高血壓危象或高血壓性腦病變, 應永久停用 Avastin 64

71 Campto Irinotecan 老年人 : 參考成人劑量 肝臟功能異常 : 1. 對於轉移性肝腫瘤或正常肝功能患者建議並不須更改劑量 2. 臨床醫師建議 : Bilirubin1.5-3 mg/dl irinotecan 劑量調整 75%(Floyd,2006) 腎臟功能異常 : 腎功能不全患者尚無相關使用評估 ; 不建議用於洗腎患者. 血液學異常 : 1. 若患者顆粒性白血球 1500/mm 3 血小板 100,000/mm 3 且因治療而產生 腹瀉完全緩解, 即可進行新療程. 2. 依據患者對於治療的耐受性, 劑量可隨之增加 mg/m 2 3. 療程需延緩 1-2 週以利治療產生的毒性回復 ; 若患者於 2 週的延遲治療並未回復, 則考慮停用 irinotecan Eloxatin Oxaliplatin 老年人 : 老年患者不需調整劑量肝臟功能異常 : Oxaliplatin 尚未對重度肝力能不良的病人進行研究. 對於肝功能異常的病人使用 Oxaliplatin 後並未觀察到有急性肝毒性加劇的現象, 在臨床試驗時對於肝功能異常的病患並無調整劑量. 65

72 腎臟功能異常 : Clcr ( ml/min ) 劑量 輕度至中度腎功能不全 不需調整 重度腎功能不全 < 20 停用 血液學異常 : 若產生 3 或 4 級胃腸毒性 4 級啫中性白血球減少症 3 或 4 級血小板 減少症 : 1. 第三期直腸癌 : 減少 Oxaliplatin 劑量為 75 mg/m 2, 延緩下次投與劑量 直至啫中性白血球 1500/mm 3 及血小板 75,000/mm 3 2. 轉移性結腸直腸癌 : 減少 Oxaliplatin 劑量為 65 mg/m 2, 延緩下次投與 劑量直至啫中性白血球 1500/mm 3 及血小板 75,000/mm 3 Emthexate Methotrexate/ M.T.X 老年人 : 參考個別之治療計畫 ; 依腎功能調整劑量 肝臟功能異常 : FDA 尚未核准劑量調整指引 一些臨床醫師使用以下方式進行劑量調整 (Floyd, 2006): 1. 膽紅素 mg/dl 或 GPT/GOT > 3 倍正常值上限 : 應調整劑量為原本之 75% 2. 膽紅素 > 5mg/dL: 避免使用 66

73 腎臟功能異常 :Aronoff, 2007 肌酸酐清除率 (ml/min) 劑量調整 10~50 正常劑量的 50% < 10 正常劑量的 30 % 血液透析 正常劑量的 50 % 連續性腎臟替代療法 (CRRT) 正常劑量的 50 % Fytosid Etoposide(VP-16) 肝功能異常及老年人無劑量調整之研究證據, 但肝功能異常使用須小心 腎臟功能異常 : Ccr:10~50ml/min 給予 75% 劑量 Ccr<10ml/min 給予 50% 劑量 骨髓抑制是此藥主要劑量限制毒性 Gemzar Gemcitabine 老年人 : 參照成人劑量 肝臟功能異常 : FDA 核準說明中, 並無包含劑量調整準則, 需小心使用 Gemcitabine 目前無使用於肝功能不全患者的相關研究, 因此目前無明確的劑量調整準則 臨床上 (Floyd, 2006) 可遵從的準則建議當 Serum bilirubin >1.6 mg/dl 時, 由 800 mg/m 2 開始使用 67

74 腎臟功能異常 : FDA 核準說明並無包含劑量調整準則, 需小心使用使用 Gemcitabine 目前無使用於腎功能不全者的相關研究, 因此目前無明確的劑量調整準則 血液學異常 : 治療時應每隔一週檢查 CBC&DC, 若出現血液毒性, 需要時可依下列準則降低劑量或停藥 ANC(ul) 血小板 (ul) 總劑量之白分比 >1000 且 > % 或 % <500 或 <50000 停藥骨髓抑制是此藥劑量限制毒性 Genataxyl Paclitaxel 過敏反應需以 corticosteroid diphenhydramine H2 blocker 於給藥前給予作為預防性給藥 廠商建議 ANC 低於 1500/μL 的病人不要給藥 發生嚴重的嗜中性白血球減少症或神經病變必須減量 20% 老年人 : 參考成人劑量 肝臟功能異常 : 依據 FDA 建議, 在肝功能正常患者第一次療程中, 給藥劑量為 175 mg/m 2, 輸注大於 3 小時 故肝功能異常患者, 其劑量調整如下 : 輸注 3 小時 68

75 GPT/GOT Bilirubin 建議劑量 <10 倍 ULN 和 1.25 倍 ULN 175 mg/m 2 <10 倍 ULN 和 倍 ULN 135 mg/m 2 <10 倍 ULN 和 倍 ULN 90 mg/m 2 10 倍 ULN 或 >5 倍 ULN 避免使用腎臟功能異常 : 關於腎功能異常的劑量調整,FDA 目前無相關文獻建議 而 2007 年 Arnoff 對於 Cl cr <50 ml/minute 患者, 也無劑量調整資料 劑量限制毒性包括骨髓抑制 過敏反應 心率不整 神經病變 Herceptin Trastuzumab 老年人 : 參考成人劑量肝臟功能異常 : 無劑量調整之需求腎臟功能異常 : 無劑量調整之需求血液學異常 : 依心臟毒性之劑量調整 : LVEF 值降低 16%( 由基礎值至正常值上限間 ) 或 LVEF 值在正常值上限之下或 LVEF 值降低 10%( 基礎值 ) 時, 暫停治療 4 週, 且每 4 週追蹤一次 LVEF 值 若 LVEF 值在 4-8 週後恢復至正常值內且 LVEF 值降低 15%( 由基礎值至正常值上限間 ), 得以繼續治療 若 LVEF 值在停用 8 週以上仍未恢復至正常值或治療期間出現 3 個以上心肌病導致治療中斷情形時, 應繼續停用 69

76 Kemocarb Carpoplatin 老年人 : 老年人劑量的調整根據 Calvert 公式老年人建議劑量計算公式以 GFR 的預估值來計算以病人 GFR (in ml/minute) 及 target AUC (in mg/ml per minute) 為基礎計 算, 劑量是 mg; 非 mg/m 2 Calvert Formula: total dose (mg) = target AUC (in mg/ml per min) [GFR (in ml/min) + 25]target AUC of 5 (range: 4 6) mg/ml per minute: 為之前已經使用過化療藥物治療病人, 今需使用 carboplatin 單一治療者最常被建議使用的劑量範圍 肝臟功能異常 : 僅極少部分由肝臟代謝, 因此肝功能不佳病患不須做調整劑量, 且目前無劑量調整準則 腎臟功能異常 : 腎功能異常劑量調整建議以 Calvert 公式之 GFR 的預測值來計算 ; 當病人 Clcr <60 ml/minute 時應降低劑量使用 ;FDA 核准建議劑量調整準則 : Baseline Clcr Initial Dose 60 ml/min 360 mg/m 2 ; 之後劑量依骨髓毒性作調整 ml/min 250 mg/m 2 ; 之後劑量依骨髓毒性作調整 ml/min 200 mg/m 2 ; 之後劑量依骨髓毒性作調整 當病人 Clcr <15 ml/minute, 在劑量調整上有太多限制, 並無 準則可使用 70

77 特殊病人之劑量調整 : 腎功能異常劑量調整已接受血液透析病患給予建議劑量的 50% 腹膜透析病患 (CAPD) 給予建議劑量的 25% 連續性腎替代性治療 (CRRT) 給予 200 mg/m 2 血液學異常 : 血小板 <50,000 cells/mm 3 或絕對嗜中性白血球數 <500 cells/mm 3 : 給予建議劑量的 75% 骨髓抑制是此藥主要劑量限制毒性 Lipo-Dox Liposomal Doxorubicin 老年人 : 參照成人劑量 微脂體藥物包覆劑型與傳統 doxorubicin hydrochloride 劑型不可直接進行劑量轉換 肝臟功能異常 : 微脂體藥物包覆劑型與傳統 doxorubicin hydrochloride 劑型不可直接進行劑量轉換 肝功能指標 劑量調整 GPT/GOT 其 ULN 的 2-3 倍建議劑量的 75% GPT/GOT 其 ULN 的 3 倍以上或 Bilirubin:1.2-3mg/dL 建議劑量的 50% Bilirubin 3.1-5mg/dL 建議劑量的 25% 71

78 Bilirubin >5 mg/dl 不建議使用 腎臟功能異常 :Doxorubicin 為肝臟代謝 膽汁排除, 故不需劑量調整之需求 血液學異常 : 血液學檢查異常劑量調整 等級 嗜中性白血球 (ANC) 血小板 劑量調整 第一級 , ,000 不需調整劑量 第二級 1000 < ,000 <75,000 待 ANC 1500 且血小板 75,000 時, 可繼續治療, 不需調整劑量 待 ANC 1500 且血小板 第三級 ,000 50,000 75,000 時, 可繼續治 療, 不需調整劑量 待 ANC 1500 並且血小 第四級 <500 <25,000 板 75,000 時, 降低 25% 劑量或不調整劑量 手足症候群 : 等級 第一級 劑量調整 若病患曾經歷第 3 級或 4 級的毒性, 延遲給藥 2 星期, 並依 72

79 之前劑量降低 25% 的劑量, 以相同投藥間隔給予 延遲給藥 2 星期或直到症狀緩解成第 0-1 級 若 2 星期之內緩解成第 0-1 級且之前無第 3-4 級的毒性時, 第二級 依之前劑量和投藥間隔給予 若 2 星期之內緩解成第 0-1 級且之前有第 3-4 級的毒性時, 依之前劑量降低 25% 並以相同投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 延遲給藥 2 星期或者直到症狀緩解成第 0-1 級, 依之前劑量 第三級 降低 25% 並以相同投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 延遲給藥 2 星期或者直到症狀緩解成第 0-1 級, 依之前劑量 第四級 降低 25% 並以相同投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 Mitomycin C M.M.C. 老年人 : 參考成人劑量 因高齡者通常生理機能較低, 骨髓功能更易受抑制, 且抑制期可能延長, 也容易發生腎功能障礙, 所以投藥時必須小心觀察病人情況, 特別注意劑量及投與間隔 肝臟功能異常 : 依據廠商建議須經常做臨床肝功能檢查, 以便隨時監控病情, 如發生有 73