高雄市立小港醫院 ( 委託高雄醫學大學經營 ) 常用化學治療處方集 目錄 Bladder Cancer... 1 Breast Cancer... 3 Colon Cancer & Rectum Cancer... 6 Esophageal Cancer... 9 Hepatoma Lu

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1 105年常用化學 治療處方集 高雄市立小港醫院 侯明 鋒院長 日期

2 高雄市立小港醫院 ( 委託高雄醫學大學經營 ) 常用化學治療處方集 目錄 Bladder Cancer... 1 Breast Cancer... 3 Colon Cancer & Rectum Cancer... 6 Esophageal Cancer... 9 Hepatoma Lung Cancer Chemotherapy Regimen 壹 非小細胞肺癌 貳 小細胞肺癌 Prostate Cancer Stomach Cancer...18 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 ) Anorexia 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 ) Hypotension( 低血壓 ) Hypocacelmia( 低血鈣 ) Hypokalemia( 低血鉀 ) Hypomagnesemia( 低血鎂 ) Insomnia( 失眠 )... 42

3 Injection site reaction( 注射部位異常反應 ) Irregular menses( 月經不規則 ) Leukopenia( 白血球低下 ) Liver dysfunction( 肝功能異常 ) 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 ) Proteinuria( 蛋白尿 ) 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 ) Tachycardia( 心搏過速 ) Weakness( 虛弱無力 ) 參考文獻... 49

4 Bladder Cancer 治療方法 Neoadjuvant or 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. Regimen2: (Ccr<50) Gemcitabine (Gemzar )1000mg/m 2 D1, D8, D15;Carboplatin 300mg/m 2 D2 Repeat every 28days for 3-4 cycles. 處方內容 Regimen3: ( CCr >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 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 參考文獻 : 1. NCCN Clinical Practice Guidelines in Oncology. Bladder Cancer. v The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group. Bamias A, Moulopoulos LA, Koutras A, Aravantinos G, Fountzilas G, Pectasides D, Kastritis E, Gika D, Skarlos D, Linardou H, Kalofonos HP, Dimopoulos MA. Cancer Jan 15;106(2): A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer. Wosnitzer MS, Hruby GW, Murphy AM, Barlow LJ, Cordon-Cardo C, Mansukhani M, Petrylak DP, Benson MC, McKiernan JM. Cancer Jan 15;118(2): Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. von der 1

5 Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. J Clin Oncol Jul 20;23(21): Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer genito-urinary group randomized phase III trial. van der Meijden AP, Brausi M, Zambon V, Kirkels W, de Balincourt C, Sylvester R; Members of the EORTC Genito-Urinary Group. J Urol Aug;166(2): Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials. M.D. Shelley, T.J. Wilt, J. Court, et al. BJU Int. 2004; 93: 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 8. 高雄市立小港醫院 (2016).Antineoplastic agents. 處方集 2

6 治療方式 Breast Cancer Chemotherapy Regime Neoadjuvant or Adjuvant Regimen 1:FEC:every 3wks for 6 cycles 5FU:600 mg/ m2 Epirubicin:75 mg/ m2 Cyclophasphamide:600 mg/ m2 Regimen 2:FEC+ Docetaxel:every 3wks for aa 3 or 4 cycles total 6 or 8 cycles 5FU:600mg/ m2 (or no) Epirubicin:75/90mg/ m2 Cyclophasphamide:600mg/ m2 Docetaxel:75/80 mg /m 2 Regimen 3:FLC:every 3wks for 6 cycles 5FU:600mg/ m2 處方內容 Lipo-Dox:30mg/ m2 Cyclophasphamide:600mg/ m2 Regimen 4:FLC+ Docetaxel:every 3wks for aa 3 or 4 cycles total 6 or 8 cycles 5FU:600mg/ m2 Lipo-Dox:30mg/ m2 Cyclophasphamide:600mg/ m2 Docetaxel 75~80 mg / m 2 Regimen 5:TEC:every 3wks for 6 cycles Taxotere:75mg/ m2 Epirubicin:75mg/ m2 Cyclophasphamide:600 mg/ m2 Regimen 6:AC:every 3wks Epirubicin:75mg/ m2 Cyclophasphamide:600mg/ m2 3

7 Regimen 7:T:every 3wks Taxotere 75 mg/m 2 Regimen 8:N:every 3wks Navelbine 25~30mg/m 2 Regimen 9:PG every 3wks Paclitaxel (Genetaxyl) 175 mg/m 2 Gemcitabine (Gemzar) mg/m 2 Regimen 10:weekly P+G Paclitaxel 80 mg/m 2 Gemcitabine (Gemzar) 800 mg/m 2 Regimen 11:Xeloda Capecitabine (Xeloda) mg/m 2 po bid 6 months Regimen 12:TG Docetaxel (Taxotere) 75~80 mg/m 2 Gemcitabine (Gemzar) 800~1000 mg/m 2 Regimen 13:weekly P Paclitaxel mg/m 2 Regimen 14:TCH Docetaxel (Taxotere) mg/m 2 Carboplatin(Kemocarb) (Ccr+25) AUC mg/m 2 Trastuzumab(Herceptin) 6 mg/kg q3wk Regimen 15:Eribulin Eribulin (Halaven) 1.4 mg/m 2 Regimen 16:CMF Cyclophasphamide 100 mg/m 2 ;Methotrexate 40 mg/m 2 ;5FU 600 mg/m 2, Q3W, 6course 標靶治療 Trastuzumab(Herceptin),Pertuzumab(Perjeta),Bevacizumab(Avastin),Kadcyla 處方內容 1. Herceptin : loading dose 8mg/kg, maintain dose: 6mg/kg,Q21d 2. Perjeta(with Herceptin and Taxotere): loading dose 840 mg,maintain dose 420 mg,q21d 3. Kadcyla : 建議劑量 3.6 mg/kg,q21d 4. Avastin(with genetaxyl): 建議劑量 5-10 mg/kg,q21d 4

8 參考文獻 : 1. 全民健康保險藥品給付規定 2. NCCN clinical practice guidelines in oncology:breast Cancer.V Levine MN, Bramwell VH, Pritchard KI, 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 1998;16: Roche H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: The FNCLCC PACS 001 trial. J Clin Oncol 2006; 24: Romond EH, Perez EZ, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med 2005;353: 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; 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: O'Brien ME, Wigler N, Inbar M, et al. 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. Ann Oncol 2004;15: Martin, Pienkowski T, Mackey J, et al: Adjuvant docetaxel for node-positive breast cancer. N Engl J. Med 2005;352: Jones S, Holmes F, O Shaughnessey J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research trial J. Clin Oncol 2009;27: 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 12. 高雄市立小港醫院 (2016).Antineoplastic agents. 處方集 5

9 Colon Cancer & Rectum Cancer 治療方式 Neoadjuvant or Adjuvant High Risk Stage II or Stage III regimen 1: 5FU:500 mg/ m2, Leucovorin:100 mg/ m2 D Cycle:Weekly for 6 of 8 weeks,3 cycles regimen 2: UFUR(Uracil(224mg)-Tegafur(100mg) Tegafur mg/ m2 /day bid /q28 天 /every 5 weeks,6 cycles regimen 3: 5FU(400 mg/ m2 ) + D5W 250ml ivd for 2hrs,5FU(2400 mg/ m2 ) + D5W 500ml ivd(keep 46hrs)every 2 weeks,12 cycles High Risk Stage II or Stage III,IV regimen 4: Capecitabine (Xeloda ) /mg/ m2 bid /q14 /every3 weeks,8 cycles (StageII 需自費 ) StageIII CRC,StageIV MCRC(1) 處方內容 FOLFOX 4 第一天 : (1)Oxaliplatin(85mg/m2) + D5W 250ml ivd (2)Leucovorin(200mg/m2) + D5W 250ml ivd (Oxaliplatin 和 Leucovorin 同時滴 2hrs:keep 125ml/hr) (3)5FU(400mg/m2) + N/S 250ml ivd for 2hr (4)5FU (600mg/m2) + N/S 500ml ivd(keep 23 ml/hr for 22hrs) 第二天 : (1)5FU(400mg/m2) + N/S 250ml ivd for 2hr (2)5FU (600mg/m2) + N/S 500ml ivd(keep 23 ml/hr for 22hrs) (3)Leucovorin(200mg/m2) + D5W 250ml ivd(keep 125ml/hr for 2hrs) (5Fu 與 Leucovorin 一起滴 ) Cycle Q 14 days StageIV MCRC(2) FOLFIRI (1) Irinotecan (180mg/m2) + NS 500ml ivd keep 2hrs (2) Leucovorin (400mg/m2) + D5W 250ml ivd keep 2hrs (3) 5-FU (400mg/m2) + D5W 250 ml ivd for 2hr (4) 5-FU (2400mg/m2) + D5W 500 ml ivd (keep 46 hrs, rate:11ml/hr) Cycle Q 14 days StageIV MCRC(3) 6

10 FOLFOXIRI (1)Eloxatin(85 mg.kg/m2) +5%G/W 250ml ivd 2 hrs (2)Campto(130mg.kg/m2) +N/S 500ml ivd 2 hours (3)5FU(400mg.kg/m2) + N/S 250ml ivd for 2 hrs (4)Leucovorin (200mg.kg/m2) + N/S 250ml ivd ( 5FU(3) & Leucovorin (4) 同時滴 2 hrs) (5)5FU(600mg.kg/m2) + N/S 500ml ivd (keep 23 ml/hr for 22 hrs ) StageIV MCRC (with target therapy) FOLFOX 4 or FOLFIRI Cycle:Q 2 wk Cetuximab 1st week 400mg/m 2 Cetuximab 2nd week 250mg/m 2 Q 1 wk or Cetuximab 1st week 400mg/m 2 Cetuximab 2nd week 500mg/m 2 Q 2 wk (KRAS:Wild type) or Bevacizumab 5 mg/ kg Q 2 wk or Aflibercept 4mg/kg Q 2wk mfolfox6 mfolfox6 Oxaliplatin 85 mg/m2 D5W 250ml 2hrs. 14days (Oxaliplatin 健保給付第三期結腸癌及轉移性結腸 直腸癌 ) mfolfox6 Leucovorin 400 mg/m2 D5W 250ml 2hrs. 14days mfolfox6 5-Fu 400 mg/m2 N/S 250ml iv bolus (1hr) 14days mfolfox6 5-Fu 2400 mg/m2 N/S 500ml 46-48hrs. 14days CC Rectal Cancer RT 處方內容 regimen 1: 5-FU + RT 5-FU 1000 mg/m2/d civi x 5 days during the first and fifth weeks of radiotherapy Concurrent radiotherapy 50.4 Gy Surgery in 4-6 weeks 5-FU 500 mg/m2/d civi d1-5 q4w x 4 cycles 參考文獻 : 1.Maindrault-Goebel F, degramont A, Louvet C, et al.evaluation of oxaliplatin dose intensity in bimonthly leucovorin and 48-hour 5-fluorouracil continuous infusion regimens (FOLFOX) in pretreated metastatic colorectal cancer. Ann Oncol 2000;11:

11 2. Venook AP, Niedzwiecki D, Lenz H-J, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-fu/leucovorin (FOLFIRI) or oxaliplatin/5-fu/leucovorin (mfolfox6) with bevacizumab or cetuximab for patients with KRAS wildtype untreated metastatic adenocarcinoma of the colon or rectum [abstract]. ASCO Meeting Abstracts 2014;32:LBA3. 3. Andre T, Louvet C, Maindrault-Goebel F, et al. CPT-11(irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continous-infusion 5-fluorouracil (FOLFIRI)for pretreated metastatic colorectal cancer. Eur J Cancer 1999;35(9): Fuchs CS, Marshall J, Mitchell E, et al. Randomized,controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007;25: Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial Lancet Oncol Van Cutsem E, Tabernero J, Lakomy R, et al. 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. J Clin Oncol 2012;30: VanCutsem E, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer:results of a large phase III study. J Clin Oncol 2001;19: Cunningham D, Pyrhonen S, James R, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. The Lancet 1998;352: Fuchs CS, Moore MR, Harker G, et al. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol 2003;21: Grothey A, Van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre,randomised, placebo-controlled, phase 3 trial. Lancet 2013;381: Cheeseman SL,Joel SP,Chester JD, et al. A modified de Gramont regimen of fluorouracil alone and with oxaliplatin for advanced colorectal cancer. Br J Cancer 2002;87: Douillard JY, Siena S, Cassidy J, et al. Randomized phase III trial of panitumumab with infusional fluorouracil leucovorin and oxaliplatin(folfox4) versus FOLFOX4 alone as first-line treatment in patient with previously untreated metastatic colorectal cancer : the PRIME study.j Clin Oncol 2010;28: Chun-Yu Lin, Joe-Bin Chen, Feng-Fan Chiang, Hwei-Ming Wang, Te-Hsin Chao, Chou-Chen Chen, Hsiu-Feng Ma, Difference between Complete Oxaliplatin Based Adjuvant Chemotherapy and Incomplete Course in Stage III Colorectal Cancer Patients in Taiwan. J Soc Colon Rectal Surgeon (Taiwan) 2016;27: 高雄市立大同醫院癌症中心化學治療處方集 8

12 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 [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 ) 處方內容 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 [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 Irinotican Irinotican (Campto) (150~180mg/ m 2 ) + N/S 250ml keep 2hrs Q2week Combine Platium [Irinotican (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 ) 9

13 參考文獻 : 1. Hsu, C.H., et al., Concurrent chemoradiotherapy for locally advanced esophageal cancer--a pilot study by using daily low-dose cisplatin and continuous infusion of 5-fluorouracil. Anticancer research, (5C): p Tepper, J., et al., Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB Journal of clinical oncology : official journal of the American Society of Clinical Oncology, (7): p Chi, K.H., et al., Elimination of dose limiting toxicities of cisplatin, 5-fluorouracil, and leucovorin using a weekly 24-hour infusion schedule for the treatment of patients with nasopharyngeal carcinoma. Cancer, (11): p Caroli-Bosc, F.X., et al., A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU)+leucovorin and bi-weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon digestive carcinomas. European journal of cancer, (15): p Working, M.R.C.O.C., Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. The Lancet, (9319): p Muro, K., et al., A phase II study of single-agent docetaxel in patients with metastatic esophageal cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, (6): p Burkart, C., et al., A phase II trial of weekly irinotecan in cisplatin-refractory esophageal cancer. Anticancer research, (4C): p Shim, H.J., et al., Phase II study of docetaxel and cisplatin chemotherapy in 5-fluorouracil/cisplatin pretreated esophageal cancer. American journal of clinical oncology, (6): p Yamasaki, M., et al., Multicenter phase I/II study of docetaxel, cisplatin and fluorouracil combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the esophagus. Oncology, (5-6): p Chen, L.T., et al., A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer. Oncology, (3): p Petrasch, S., et al., Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. British journal of cancer, (4): p Lin, C.C., et al., Multifractionated paclitaxel and cisplatin combined with 5-fluorouracil and leucovorin in patients with metastatic or recurrent esophageal squamous cell carcinoma. Anti-cancer drugs, (6): p Spiridonidis, C.H., et al., A phase II evaluation of high dose cisplatin and etoposide in patients with advanced esophageal adenocarcinoma. Cancer, (10): p Kok, T.C., et al., Cisplatin and etoposide in oesophageal cancer: a phase II study. Rotterdam Oesophageal Tumour Study Group. British journal of cancer, (6): p

14 Hepatoma 治療方式 Chemotherapy drugs: maybe used single or in combination(palliative) TACE (1)Epirubicin (10-30mg)/m 2 (2)Mitomycin C(2~10mg)/m 2 (3)Cisplatin(2-40mg)/m 2 處方內容 Systemic Oral Chemotherapy (1) UFUR 1# - 2#/day q12h Target therapy(adjuvan Palliative) (1) Nexavar(sorafenib) 1# - 2#/day q12h 參考文獻 : 1. 國家衛生研究院肝癌小組專家共事會議結論報告 AASLD practice guideline Hepatology NCCN Clinical Practice in Oncology: Hepatobiliary Cancers V Gaba RC. Chemoembolization practice patterns and technical methods among interventional radiologists: results of an online survey.ajr Am J Roentgenol Mar;198(3): Llovet JM, et al. N Engl J Med. 2008;359: Cheng A, et al. Lancet Oncol. 2009;10: 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 8. Martin, M, Lluch, A, Segui, M.A, Ruiz, A, Ramos, M, Adrover, E, Rodriguez-Lescure, A, Grosse, R, Calvo, L, Fernandez-Chacon, C, Roset, A, Anton, M, Isla, D, Martinez del Prado, P, Iglesias, L, Zaluski1, J, Arcusa, A, M.Lopez-Vega, J, Munoz, M, Mel, J.R. (2006). Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regim. Annals of Oncolog, 17,

15 Lung Cancer Chemotherapy Regimen 壹 非小細胞肺癌 (NSCLC) 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 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 Q28days 4-6 cycles CCr 60 CCr<60 CCr 60 CCr<60 Vinorelbine (Navelbine ) ORAL 20mg Q3W 前三次依體表面積每週 *Paclitaxel (Genetaxyl ) 給藥 60mg/m 2 一次, 第四次開始增加每週 80mg/m 2 一次 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 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 Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles Q21days 4-6 cycles Q28days 4-6 cycles Q28days 4-6 cycles CCr 60 CCr<60 CCr 60 CCr<60 CCr 60 CCr<60 12

16 藥物種類 劑量 間隔治療時間備註 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 Q21days 4-6 cycles Q21days 4-6 cycles Q21days 4-6 cycles 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 Gefitinib (Iressa ) 250 mg QD 需經健保事前審查核准後使用 Erlotinib (Tarceva ) 150 mg QD 需經健保事前審查核准後使用 Afatinib (Giotrif ) 40 mg QD 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 * 可當 adjuvant chemotherapy 參考文獻 : 1. Hanna NH, Sheperd FA, Fossella FV, et al. Randomized phase III study of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004;22: Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage NSCLC. J Clin Oncol 2008;26: Okamoto I1, Aoe K, Kato T, Hosomi Y, Yokoyama A et al Pemetrexed and carboplatin followed by pemetrexed maintenance therapy in chemo-naïve patients with advanced nonsquamous non-small-cell lung cancer. Invest New Drugs Oct;31(5): Rodrigues-Pereira J, Kim JH, Magallanes M et al. A randomized phase 3 trial comparing pemetrexed/carboplatin and docetaxel/carboplatin as first-line treatment for advanced, nonsquamous non-small cell lung cancer. J Thorac Oncol Nov;6(11): de Castria TB1, da Silva EM, Gois AF, Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst Rev Aug 16;8 5. de Castria TB1, da Silva EM, Gois AF, Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer. Cochrane Database Syst Rev Aug 16;8: 6. Cardenal F, Lopez-Cabrerizo MP, Anton A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 1999;17:

17 7. Sandler AB, Nemunaitis J, Denham C, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 2000;18: Smit EF, van Meerbeeck JP, Lianes P, et al. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group-EORTC J Clin Oncol 2003;21: Ohe Y, Ohashi Y, Kubota K, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced nonsmall-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol 2007;18: Ramalingam S1, Belani CP. Oncology (Williston Park) Jul;18(8 Suppl 5):21-6. Carboplatin/gemcitabine combination in advanced NSCLC. 11. Fossella F, Periera JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21(16): Kelly K, Crowley J, Bunn PA, et al. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: A Southwest Oncology Group trial. J Clin Oncol 2001;19: Horvath L1, Boyer M, Clarke S, et al, Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer. Lung Cancer May;32(2): Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small cell lung cancer previously treated with platinumcontaining chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000;18: Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 2002;346: Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med 2004;350: Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: A Southwest Oncology Group Phase II Study, SWOG J Clin Oncol 2002;20: Vokes EE, Senan S, Treat JA, Iscoe NA. PROCLAIM: A phase III study of pemetrexed, cisplatin, and radiation therapy followed by consolidation pemetrexed versus etoposide, cisplatin, and radiation therapy followed by consolidation cytotoxic chemotherapy of choice in locally advanced stage III 14

18 Lung Cancer Chemotherapy Regimen 貳 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 Cyclophosphamide (Endoxan ) 500mg/m2 D1 +Epirubicin (Pharmorubicin ) 50mg/m2 D1 +Cisplatin 50mg/m2 D1 Cyclophosphamide (Endoxan ) 500mg/m2 D1 + Epirubicin (Pharmorubicin ) 50mg/m2 D1 +Carboplatin (AUC=5) D1 Topotecan 1.5mg/m 2 D1 Q21-28 days 6 cycles Ccr 60 Q21-28 days 6 cycles Ccr<60 Q21-28 days 6 cycles Ccr 60 Q21-28 days 6 cycles Ccr<60 Q21 days 4-6 cycles 參考文獻 : 1. Saito H, Takada Y, Ichinose Y, et al. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group J Clin Oncol 2006;24(33): Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol 2001;12(9): Sundstrom S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superiorto cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer:results from a randomized phase III trial with 5 years follow-up. J Clin Oncol 2002;20(24): Ihde DC, Mulshine JL, Kramer BS, et al. Prospective randomized comparison of highdose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol 1994;12(10): Ihde DC, Mulshine JL, Kramer BS, et al. Prospective randomized comparison of highdose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol 1994;12(10): Evans WK, Shepherd FA, Feld R, et al. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol 1985;3(11):

19 6. Bonomi P Platinum/etoposide therapy in non-small cell lung cancer. Oncology. 1992;49 Suppl 1: Review. 7. Birch R, Weaver CH, Hainsworth JD et al. A randomized study of etoposide and carboplatin with or without paclitaxel in the treatment of small cell lung cancer. Semin Oncol Aug;24(4 Suppl 12):S S Schmittel A, Fischer von Weikersthal L, Sebastian M et al. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol Apr;17(4): von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17(2): O'Brien ME, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006;24(34): Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007;25(15):

20 Prostate Cancer CRPC Case 適用 (castration resistance prostate cancer) 處方內容 Systemic Regimen1: Docetaxel (Taxotere ) 75mg/m 2 + Prednisolone 1# bid 5days/ 21~ Q28d,6~8 course 參考文獻 : 1. Tannock IF, Fizazi K, Ivanov S, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol 2013;14(13): Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351(15): Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, et al. 2-Weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol 2013;14(2): Machiels JP, Mazzeo F, Clausse M, et al. Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer. J Clin Oncol 2008;26(32): Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus Cisplatin Compared with Etoposide plus Cisplatin for Extensive Small-Cell Lung Cancer. Engl J Med 2002;346: Papandreou CN, Daliani DD, Thall PF, et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patientswith fully characterized small-cell carcinoma of the prostate. J Clin Oncol 2002;20(14):

21 Stomach Cancer 治療方式 Neoadjuvant or Adjuvant 處方內容 RESECTABLE ECF Preoperative Epirubicin 50 mg/m 2 iv bolus d1 q3w 3 cycles Cisplatin (Kemoplat) 60 mg/m 2 iv d1 q3w 3 cycles 5-FU 200 mg/m 2 /d civi 24 weeks Adjuvant Epirubicin 50 mg/m 2 iv bolus d1 q3w 3 cycles Cisplatin (Kemoplat) 60 mg/m 2 iv d1 q3w 3 cycles 5-FU 200 mg/m 2 /d civi 24 weeks FOLFOX 4 Leucovorin 200 mg/m 2 iv over 2 hrs before 5-FU, d1 and d2, q2w 12 cycles 5-FU 400 mg/m 2 iv bolus and then 600 mg/m2 iv over 22 hrs, d1 and d2, q2w 12 cycles Oxaliplatin (Eloxatin) 85 mg/m 2 iv d1, q2w 12 cycles Oral TS1:40-60mg/BID x 28 days, 14 days off (Q 6 weeks) 5,6 UNRESECTABLE or METASTATIC DCF Docetaxel (Taxotere) 75 mg/m 2 iv d1 q3w 8 cycles Cisplatin (Kemoplat) 75 mg/m 2 iv d1 q3w 8 cycles 5-FU 750 mg/m 2 /d civi d1-5 q3w 8 cycles ECF Epirubicin 50 mg/m 2 iv bolus d1 q3w x 8 cycles Cisplatin (Kemoplat) 60 mg/m 2 iv d1 q3w x 8 cycles 5-FU 200 mg/m 2 /d civi x 6 months ECX Epirubicin 50 mg/m 2 iv bolus d1 q3w 8 cycles Cisplatin (Kemoplat) 60 mg/m 2 iv d1 q3w 8 cycles Capecitabine (Xeloda) 625 mg/m 2 po bid 6 months EOX Epirubicin 50 mg/m 2 iv bolus d1 q3w 8 cycles Oxaliplatin (Eloxatin) 130 mg/m 2 iv over 2 hours d1 q3w 8 cycles Capecitabine (Xeloda) 625 mg/m 2 po bid 6 months FLO Oxaliplatin (Eloxatin) 85 mg/m 2 iv over 2 hours d1 q2w Leucovorin 200 mg/m 2 iv over 2 hours d1 q2w 18

22 5-FU 200 mg/m 2 civi over 24 hours q2w Paclitaxel 80 mg/m 2 Ⅳ on Days 1,8 and 15 cycled every 28 days 7 FOLFOX 4 Leucovorin 200 mg/m 2 iv over 2 hrs before 5-FU, d1 and d2, q2w 12 cycles 5-FU 400 mg/m 2 iv bolus and then 600 mg/m2 iv over 22 hrs, d1 and d2, q2w 12 cycles Oxaliplatin (Eloxatin) 85 mg/m 2 iv d1, q2w 12 cycles XELOX&XP Capecitabine (Xeloda) 1000 mg/m 2 po bid 14 days q3w 8 cycles Oxaliplatin (Eloxatin) 130 mg/m 2 iv over 2 hrs d1 q3w 8 cycles Cisplatin 80mg/m 2 iv over 4hrs d1 q3w 8 cycles UFUR 1# po bid CCRT Initial 5-FU 425 mg/m 2 /d iv & Leucovorin 20 mg/m 2 /d iv, d1-5 處方內容 One month later 5-FU 400 mg/m 2 /d iv & Leucovorin 20 mg/m 2 /d iv, d1-4 and last 3 days of RT Radiotherapy 1.8 Gy/d to 45 Gy One month after completion of RT 5-FU 425 mg/m 2 /d iv, d1-5, q4w 2 cycles Leucovorin 20 mg/m 2 /d iv, d1-5, q4w 2 cycles Target therapy HER2 positive Trastuzumab 8mg/kg iv on Day 1 of cycle 1,then Trastuzumab 6mg/kg iv every 21 days 處方內容 Capecitabine 1000mg/m 2 po bid on Day 1-14 every 21 days or 5FU 800mg/m 2 iv continue infection on Day 1-5 every 21 days Cisplatin 80mg/m 2 iv on Day 1 every 21 days 參考文獻 : 1. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355: Sumpter K, Harper-Wynne C, Cunningham D, et al. Report of two protocol planned interim analyses in a randomized multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer 2005;92: Ychou M, Boige V, Pignon J-P, et al. Perioperative chemotherapy compared with surgery alone 19

23 for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol 2011;29: Guimbaud R, Louvet C, Ries P, et al. 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. J Clin Onc 2014;32: Sasako M, Sakuramoto S, Katai H, et al. 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. J Clin Oncol 2011; 29: Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant Chemotherapy for Gastric Cancer with S-1, an Oral Fluoropyrimidine. The NEW ENGLAND JOURNAL of MEDICINE 2007; 357: Hironaka S, Ueda S, Yasui H, et al. Randomized, openlabel, phaseⅢ study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 2013; 31:

24 藥物產品規格 商品名 學名 劑量 5-Fluorouracil (5-FU) 5-Fluorouracil 500mg/10mL/Vial 1g/20 ml/vial Kemoplat Cisplatin 50mg/ 100ml/Bot Alimta Pemetrexed 500mg/Vial Avastin Bevacizumab 100mg/ 4mL/ Vial Campto Irinotecan 100mg/5ml/Vial Eloxatin Oxaliplatin 50 mg/10ml/vial Emthexate Methotrexate (M.T.X) 500mg/ 5ml Amp Erbitux Cetuximab 100mg/20mL/Vial Fytosid Etoposide(VP-16) 100mg/5ml/ Vial Gemzar Gemcitabine 200mg/Vial Genataxyl Paclitaxel 30mg/5ml/Vial Herceptin Trastuzumab 440mg/Vial Kemocarb Carboplatin 150mg/15ml/Vial Lipo-Dox Liposomal Doxorubicin 20mg/10mL/Vial Mitomycin Mitomycin C ( M.M.C.) 2mg/Vial Navelbine Vinorelbine tartrate 50mg/5ml/Vial Pharmorubicin Epirubicin 10mg/Vial Endoxan Cyclophosphamide 500mg/Vial 200mg/Vial Taxotere (20mg) Docetaxel (20mg) 20mg/0.5ml/Vial Taxotere (80mg) Docetaxel (80mg) 80mg/2ml/Vial Kadcyla Trastuzumab Emtansine 100mg/Vial Perjeta Pertuzumab 420mg/14mL/Vial Zaltrap Aflibercept 100mg/4mL/Vial 口服 Iressa Gefitinib 250 mg/tab Tarceva Erlotinib 150 mg/tab Giotrif Afatinib 40 mg/tab Xeloda Capecitabine 500mg/Tab UFUR Tegafur/ uracil 100mg/224mg/Cap 21

25 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 Clcr (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 >100000cell/mm 3 22

26 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 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 Campto Irinotecan 老年人 : 參考成人劑量 肝臟功能異常 : 23

27 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. 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 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 % 24

28 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 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 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 25

29 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 Clcr< 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 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 60 ml/min Initial Dose 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 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 26

30 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% 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 血小板 劑量調整 (ANC) 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 第三級 ,000 50,000 待 ANC 1500 且血小板 75,000 時, 可繼續治療, 不需調整劑量 第四級 <500 <25,000 待 ANC 1500 並且血小板 75,000 時, 降低 25% 劑量或不調整劑量 27

31 手足症候群 : 等級劑量調整第一級若病患曾經歷第 3 級或 4 級的毒性, 延遲給藥 2 星期, 並依之前劑量降低 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, 依之前劑量和投藥間隔給予 第二級 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, 依之前劑量降低 25% 並以相同第三級投藥間隔給予 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, 依之前劑量降低 25% 並以相同第四級投藥間隔給予 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, 如發生有異常時, 須做減 量或停藥等適當處理 另長期使用時, 副作用可能增強, 也可能會延長, 因此須慎重投藥 腎臟功能異常 : 依據廠商建議須經常做臨床腎功能檢查, 以便隨時監控病情, 如發生有異常時, 須做減 量或停藥等適當處理 另長期使用時, 副作用可能增強, 也可能會延長, 因此須慎重投藥 血液學檢查 : 可能會引起骨髓造血機能抑制, 如全部血球減少 白血球減少 嗜中性白血球減少 血 小板減少 出血和貧血, 依據廠商建議須經常做臨床血液檢查, 以便隨時監控病情, 如發生 有異常時, 須做減量或停藥等適當處理 另長期使用時, 副作用可能增強, 也可能會延長, 因此須慎重投藥 列出可能發生的副作用, 病人應接受密切的觀察, 如有異狀應做適當處置, 如降低劑量 或終止用藥, 如下表 : 5% 5% > % 發生率不明 腎臟蛋白尿血尿 水腫 高血壓 肝臟 腸胃系統厭食 噁心 / 嘔吐口炎腹瀉

32 過敏皮疹泌尿系統 ( 膀胱灌洗 ) 膀胱炎 血尿膀胱萎縮其他身體不適禿髮骨髓抑制是此藥主要劑量限制毒性 Navelbine Vinorelbine 老年人 : 參考成人劑量 肝臟功能異常 : FDA 核准之指引如下 : 肝功能不全者給予 Vinorelbine 治療時, 應小心謹慎 若使用 Vinorelbine 治療期間產生高膽紅素血症, 應視其膽紅素血中濃度而調整劑量, 劑量調整方式如下 : Total Bilirubin (mg/dl) 劑量調整 2.0 正常劑量的 100 % 2.1 to 3.0 正常劑量的 50 % >3.0 正常劑量的 25 % 腎臟功能異常 : 不需調整劑量 血液學檢查 : 治療當天顆粒性白血球計數 (cells/mm 3 ) 劑量調整 1,500 正常劑量的 100 % 1,000 to 1,499 正常劑量的 50 % <1000 暫停給藥治療期間若病人因顆粒性白血球低下 (granulocytopenic) 而發燒 產生敗血症或因顆粒 性白血球低下而連續暫停兩次劑量之治療, 隨後的 vinorelbine 治療劑量調整如下 : 治療當天顆粒性白血球計數 (cells/mm 3 ) 劑量調整 1,500 正常劑量的 75% 1,000 to 1,499 正常劑量的 37.5% <1,000 暫停給藥白血球低下是此藥主要劑量限制毒性 Pharmorubicin Epirubicin 老年人 : 老年女性患者其 Epirubicin 的血漿清除率減少 35% 然而對降低起始劑量的方面並沒有具體的建議, 但特別應注意老年患者的毒性監督和劑量調整 ( 尤其是 70 歲以上女性 ) 肝臟功能異常 : FDA 核准的建議如下列準則 ( 根據臨床試驗資料 ): 29

33 Bilirubin/GOT 劑量調整 1.2-3mg/dl 或 UNL 的 2-4 倍建議起始劑量的 50% 大於 3mg/dl 或 UNL 的 4 倍建議起始劑量的 25% 嚴重肝損害禁用腎臟功能異常 FDA 核准建議 : 重度腎功能損害 ( 血清肌酐酸 >5mg/dl) 的病人, 應考慮較低的劑量 Aronoff( 2007 ) 建議 Clcr <50 ml/minute. 不作劑量調整需要 血液學異常 : 1. 當病患血小板計數是在 <50,000/ mm 3, ANC <250/ mm 3 或有 neutropenic fever, 應該減少隨後週期的第一天藥量到目前劑量的 75% 下次療程的第 1 天化療, 應等到病患血小板數大於或等於 100,000/ mm 3 或 ANC 大於或等於 1500/ mm 3, 才執行 2. 在病患接受 Epirubicin 治療的第 1 天及第 8 天中, 假如病患血小板數是在 75,000 to 100,000/ mm 3 及 ANC 在 1000 to 1499/ mm 3, 則第 8 天的劑量只要第一天的 75% 即可 3. 若病患血小板數小於 75,000/ mm 3 或 ANC 小於 1000/ mm 3 時, 則第 8 天劑量可省略不做 骨髓抑制是此藥短期劑量限制毒性 心臟損傷是長期劑量限制毒性, 最高累積劑量為 900mg/ m2 Endoxan Cyclophosphamide 老年人 : 針對個人情況做調整, 建議開始及維持劑量 :1-2mg/kg/day; 依照 renal clearance 調整 肝臟功能異常 : Cyclophosphamide 的藥物動力學在肝功能不良的病人並沒有明顯的改變 FDA 核准的建議劑量並不包括肝功能劑量的調整準則. 下列的準則曾被一些臨床醫師採用 (Floyd, 2006): Serum bilirubin mg/dl 或 GPT/GOT >3 倍 ULN: 使用 75% 的劑量 Serum bilirubin >5 mg/ml: 避免使用 腎臟功能異常 : FDA 所核准的建議劑量沒有足夠的證據去建議在腎功能的劑量調整. 下列的準則曾被一些臨床醫師採用 (Aronoff, 2007): 兒童或成人 :Clcr <10 ml/minute: 使用正常劑量的 75% 血液透析的作用 : 中度透析 (20% to 50%): 透析後給予 50% 的劑量 連續可活動性腹膜透析 (CAPD) : 給予正常劑量的 75% 連續性腎臟替代療法 (CRRT): 給予正常劑量的 100% 骨髓抑制和出血性膀胱炎是此藥劑量限制毒性, 而骨髓抑制是最主要的 Taxotere Docetaxel 所有的病人必須於給藥前給予皮質類固醇作為預防性給藥, 以降低過敏反應和體液滯留的嚴重度 老年人 : 參照成人劑量 肝臟功能異常 : 1. 當 Total bilirubin> 正常值上限或 GOT/GPT>1.5 倍且 Alkaline phosphatase(alp >2.5 倍正常值上限時, 不建議使用 docetaxel 30

34 2. 其它文獻建議 Floyd, 2006 : GOT/GPT>ULN 的 倍時, 將劑量調整為正常劑量的 75% GOT/GPT>ULN 的 6 倍時, 需依照臨床上的評估 腎臟功能異常 :Docetaxel 只有少部分由腎排除, 不需調整劑量 血液學異常 : 依毒性調整劑量 : 1.Docetaxel 引起的毒性包含 febrile neutropenia,neutrophils 持續一星期以上低於 500 cells/mm 3, 嚴重或蓄積性皮膚反應 2. 乳癌患者, 若起始劑量為 100 mg/m 2, 其血液學檢查異常時, 應將劑量降低為 75 mg/m 2 若副作用持續, 應將劑量降至 55 mg/m 2 或停用 若末稍神經病變大於 3 級時應停用 3. neutrophils 小於 1500 cells/mm 3 的患者不建議使用 docetaxel 劑量限制毒性包括骨髓抑制 過敏反應 肝損傷 31

35 常見副作用 Gemcitabine 副作用 >10% Peripheral edema (20%), edema (13%), Pain (10% to 48%), fever (30% to 41%), somnolence (5% to 11%), Rash (24% to 30%), alopecia (15% to 18%), pruritus (13%), Nausea/vomiting (64% to 71%; grades 3/4: 1% to 13%), constipation (10% to 31%), diarrhea (19% to 30%), stomatitis (10% to 14%),Anemia (65% to 73%; grade 4: 1% to 3%), leukopenia (62% to 71%; grade 4: 1%), neutropenia (61% to 63%; grade 4: 6% to 7%), thrombocytopenia (24% to 47%; grade 4: 1%), hemorrhage (4% to 17%; grades 3/4: <1% to 2%); myelosuppression is the dose-limiting toxicity, Transaminases increased (67% to 78%; grades 3/4: 1% to 12%), alkaline phosphatase increased (55% to 77%; grades 3/4: 2% to 16%), bilirubin increased (13% to 26%; grades 3/4: <1% to 6%), Proteinuria (10% to 45%; grades 3/4: <1%), hematuria (13% to 35%; grades 3/4: <1%), BUN increased (8% to 16%; grades 3/4: 0%), Dyspnea (6% to 23%), Flu-like syndrome (19%), infection (8% to 16%; grades 3/4: <1% to 2%) 副作用 1% to 10% Injection site reactions (4%), Paresthesia (2% to 10%), Creatinine increased (2% to 8%), Bronchospasm (<2%) 副作用 <1% Adult respiratory distress syndrome, anaphylactoid reaction, anorexia, arrhythmias, bullous skin eruptions, cellulitis, cerebrovascular accident, CHF, chills, cough, desquamation, diaphoresis, gangrene, GGT increased, headache, hemolytic uremic syndrome (HUS), hepatotoxic reaction (rare), hypertension, insomnia, interstitial pneumonitis, liver failure, malaise, MI, peripheral vasculitis, petechiae, pulmonary edema, pulmonary fibrosis, radiation recall, renal failure, respiratory failure, rhinitis, sepsis, supraventricular arrhythmia, weakness 5-Fluorouracil (5-Fluorouracil (5-FU)) 副作用 Angina, myocardial ischemia, nail changes,acute cerebellar syndrome, confusion, disorientation, euphoria, headache, nystagmus, Alopecia, dermatitis, dry skin, fissuring, palmar-plantar erythrodysesthesia syndrome, pruritic maculopapular rash, photosensitivity, vein pigmentations, Anorexia, bleeding, diarrhea, esophagopharyngitis, nausea, sloughing, stomatitis, ulceration, vomiting, Agranulocytosis, anemia, leukopenia, pancytopenia, thrombocytopenia Myelosuppression: (Onset: 7-10 days;nadir: 9-14 days;recovery: days), Thrombophlebitis,Lacrimation, lacrimal duct stenosis, photophobia, visual changes, Epistaxis, Anaphylaxis, generalized allergic reactions, nail loss Epirubicin 副作用 >10% Lethargy (1% to 46%),Alopecia (69% to 96%), Amenorrhea (69% to 72%), hot flashes (5% to 39%), Nausea/vomiting (83% to 92%; grades 3/4: 22% to 25%), mucositis (9% to 59%; grades 3/4: 9%), diarrhea (7% to 25%), Leukopenia (50% to 80%; grades 3/4: 2% to 59%), neutropenia (54% to 80%; grades 3/4: 11% to 67%; nadir: days; recovery: 21 days), anemia (13% to 72%; grades 3/4: 6%), thrombocytopenia (5% to 49%; grades 3/4: 5%), Injection site reactions (3% to 20%; grades 3/4: <1%), Conjunctivitis (1% to 15%), Infection (15% to 22%; grades 3/4: 2%) 32

36 副作用 1% to 10% LVEF decreased (asymptomatic; delayed: 1% to 2%), HF (0.4% to 1.5%), Fever (1% to 5%), Rash (1% to 9%), skin changes (1% to 5%), Anorexia (2% to 3%), Neutropenic fever (grades 3/4: 6%) 副作用 <1% Abdominal pain, acute lymphoid leukemia (ALL), acute myelogenous leukemia (AML), anaphylaxis, ascites, atrioventricular block, bradycardia, bundle-branch block, cardiomyopathy, chills, dehydration, dyspnea, ECG abnormalities, esophagitis, hepatomegaly, hyperpigmentation (oral mucosa, nails, skin), hypersensitivity, myelodysplastic syndrome, photosensitivity, premature menopause, premature ventricular contractions, pulmonary edema, pulmonary embolism, radiation recall, shock, sinus tachycardia, stomatitis, ST-T wave changes (nonspecific), tachyarrhythmias, thromboembolism, thrombophlebitis, transaminases increased, urticaria, ventricular tachycardia Cyclophosphamide 副作用 >10% Alopecia (40% to 60%), May cause sterility, Nausea and vomiting, anorexia, diarrhea, mucositis, stomatitis, acute hemorrhagic cystitis (7% to 40%), Thrombocytopenia and anemia are less common than leukopenia (ALL)Onset: 7 days;nadir: days ;Recovery: 21 days 副作用 1% to 10% Facial flushing, Headache, Skin rash, Nasal congestion occurs when I.V. doses are administered too rapidly; patients experience runny eyes, rhinorrhea, sinus congestion, and sneezing during or immediately after the infusion. 副作用 <1% High-dose therapy may cause cardiac dysfunction manifested as CHF; cardiac necrosis or hemorrhagic myocarditis has occurred rarely, but may be fatal. Interstitial pneumonitis and pulmonary fibrosis are occasionally seen with high doses. Cyclophosphamide may also potentiate the cardiac toxicity of anthracyclines. Other adverse reactions include anaphylactic reactions, darkening of skin/fingernails, dizziness, hemorrhagic colitis, hemorrhagic ureteritis,hepatotoxicity, hyperuricemia, hypokalemia, jaundice, malaise, neutrophilic eccrine hidradenitis, radiation recall, renal tubular necrosis, secondary malignancy (eg, bladder carcinoma), SIADH, Stevens-Johnson syndrome, toxic epidermal necrolysis, weakness. Docetaxel 副作用 >10% Fluid retention (13% to 60%; dose dependent),neurosensory events (20% to 58%; including neuropathy), fever (31% to 35%), neuromotor events (16%),Alopecia (56% to 76%), cutaneous events (20% to 48%), nail disorder (11% to 41%),Stomatitis (19% to 53%; severe 1% to 8%), diarrhea (23% to 43%; severe: 5% to 6%), nausea (34% to 42%), vomiting (22% to 23%), Neutropenia (84% to 99%; grade 4: 75% to 86%; onset: 4-7 days, nadir: 5-9 days, recovery: 21 days; dose dependent), leukopenia (84% to 99%; grade 4: 32% to 44%), anemia (65% to 94%; dose dependent; grades 3/4: 8% to 9%), thrombocytopenia (8% to 14%; grade 4: 1%; dose dependent), febrile neutropenia (6% to 12%; dose dependent), Transaminases increased (4% to 19%), Weakness (53% to 66%; severe 13% to 18%), myalgia (3% to 23%), Pulmonary events (41%), Infection (1% to 34%; dose dependent), hypersensitivity (1% to 21%; with premedication 15%) 33