慢性肝病时抗肿瘤药物的应用推荐.docx

1、慢性肝病时抗肿瘤药物的应用推荐慢性肝病患者常用抗肿瘤药物应用推荐（文献来源：Periez-Prraga L, Martnez-Lpez I, Ventayol-Bosch P, Puigvents Latorre F, Delgado-Snchez O. Drug dosage recommendations in patients with chronic liver disease. Rev Esp Enferm Dig 2012; 104: 165-184.）Drug (references) Huet and Krhenbhl (11,12) category EH Metabolis

2、m Q0 PB (%) Recommendation Anastrazole Prod Info Arimidex, 2010 (27) 阿那曲唑4 Not known未知 N-dealkylation, hydroxylation (CYP), glucuronidation N-脱烷基作用，羟基化作用CYP)，糖脂化作用0.95 45 No adjustment required不需要调整 Letrozole* (9) 来曲唑3 0.03 Liver metabolism (CYP3A4, 2D6) 肝代谢(CYP3A4, 2D6)0.95 60 Patients with cirrhos

3、is or with Child-Pugh C index reduced by 50% dose 肝硬化的病人或者CPT C的病人减少50%剂量Tamoxifen (9) 他莫昔芬3 0.9 5.0-9.0 Monitor liver function 监测肝功能Mercaptopurine* (9)巯基嘌呤2 0.46 Extensive liver metabolism: xantino-oxidasa 广泛肝代谢：黄嘌呤氧化酶0.9 19 Monitor liver function监测肝功能 Azathioprine Prod Info Imurel, 2007 (27) 硫唑嘌呤2

4、 0.4 Oxidation 氧化作用30 Precaution 慎用Bicalutamide* (9) 比卡鲁胺2 0.34 Oxidation (CYP), glucuronidation 氧化作用(CYP), 糖脂化（作用）198 Monitor liver function. If transaminases three times normal or bilirubin value is recommended to avoid treatment监测肝功能如果转氨酶是正常的三倍或者胆红素值提供的建议避免治疗Chlorambucil (8) 氯氨布西3 5% 广泛肝代谢：CYP2C8

5、，少量由CYP3A4代谢胆汁排泄: 5%0.95 95 Transaminase转氨酶Total bilirubin总血红素Dose level 24h Infusion 2 Nv 1.5mg/dL135mg/m22-10 Nv1.5 mg/dL100 mg/m2 10 Nv 7.5 mg/dLnot administer不给药3 h Infusion 10 Nv 1.25 Nv175 mg/m2 10 Nv1.26-2 Nv 135 mg/m2 10 Nv 5 Nvnot administer Nv: normal valueIrinotecan* Prod Info Irinotecan

6、Hospira, 2005 (27) 伊立替康3 0.22 Esterases, glucuronidation, CYP3A4 Biliar excretion: 25% 酯酶，糖脂化，CYP3A4胆汁排泄：25%0.75 65 Total bilirubin level Dose1.1-1.5 normal value350 mg/m21.5 normal value200 mg/m25 normal valuecontraindicated总胆红素水平 剂量1.1-1.5倍正常值350 mg/m2 1.5倍正常值200 mg/m2 5倍正常值禁用Busulfan* Prod Info B

7、usilvex, 2008 (27) 白消安3 0.21 Oxidation, sulfation 氧化作用, 硫化作用1 30 Precaution 慎用Bleomycin* (9)博来霉素3 0.04 Hydrolysis 水解作用0.7No adjustment required不需要调整Carboplatin* Prod Info Carboplati-no Teva, 2009 (27) 卡波铂3 0.012 0.25 20 No adjustment required. If overdose occurs hepatotoxicity 不需要调整, 如果过量则发生肝毒性Cyclo

8、phosphamide* (8) 环磷酰胺3 0.04 Hydroxylation (CYPs 2B6, 2C19, 2C9, 3A4) 羟基化(CYPs 2B6, 2C19, 2C9, 3A4) 0.9 15 If total bilirubin 3 mg/ml reduce dose by 25%，Monitor liver function 如果总胆红素 3 mg/ml，减少25%的剂量，监测肝功能。Doxorubicin* Prod Info Doxorubicin Hydrochloride, 2003 (27) 多柔比星（阿霉素）1 0.73 Plasmatic and liver

9、 metabolism (doxorubicinol), sulfation, glucuronidation Biliar excretion: 50-80% 胞质和肝脏代谢(阿霉素醇)，硫化作用，糖脂化胆汁排泄: 50-80%0.95 80 Reduced dose: Serum bilirubin (mg/dL) 1.2 - 3.03.1 - 5.0血清胆红素(mg/dL) 1.2 - 3.0 3.1 - 5.0 Dose reduction(%)5075减少剂量.5075Epirubicin* Prod Info Epirubicina Accord, 2010 (27) 表柔比星1

10、0.89 Reduction Biliar excretion: 40%还原胆汁排泄:40% 0.9 85 Reduced dose: Serum bilirubin (mg/dL) 1.2-3.03.1-5.0血清胆红素(mg/dL)降低(%): 1.2-3.03.1-5.0 ,Dose reduction (%)5075减少剂量5075Fluorouracil* (9)氟尿嘧啶1 0.71 Dihydropyrimidine dehydrogenase二氢嘧啶脱氢酶0.95 94 If total bilirubin 5 mg/dL: 100% dose。If total bilirubi

11、n 5 mg/dL: avoid。In cirrhotic patients recommended starting dose of 50% and increase as liver toxicity 如果总胆红素 5 mg/dL:用100%剂量。如果总胆红素 5 mg/dL：避免使用。肝硬化病人初始剂量50%正常剂量，加强肝毒性。Etoposide* (9) 依托泊苷3 0.02 Extensive liver metabolism: CYP3A4, glucuronidation and sulfation. Biliar excretion: 10%. 广泛肝代谢: CYP3A4,

12、糖脂化和硫化作用. 胆汁排泄 3.1 and AST 180) Monitor liver function is recommended. 如果总胆红素1.5-3 mg/dL或AST 60-180 U/L减少50%，失代偿的肝病病人禁忌.（总胆红素 3.1和AST 180），建议监测肝功能.Cytarabine* (9) 阿糖胞苷2 0.55 Cytidine deaminase胞核嘧啶核苷脱氨酶0.9 13 If total bilirubin 2 mg/ml reduce dose by 50% Monitor liver function 若总胆红素 2 mg/ml，减少50%的剂量，

13、监测肝功能Dacarbazine* 达卡巴嗪3 0.04 Extensive liver metabolism causing some metabolites with cytotoxic activity, being eliminated in the urine 18-63% 广泛的肝代谢导致一些代谢产物的细胞毒活性，在尿液中的消除18-63%0.3 5 * Maintenance dose:CP A: 50% of normal dose CP B: 25% of normal dose CP C: drug monitoring 维持用量: CP A:50%的正常量CP B: 25

14、%的正常量CP C: 药物监测Docetaxel* (9) 多西他赛2 0.43 Oxidation (CYP3A4). Biliar excretion: 75% 氧化作用(CYP3A4)，胆汁排泄：75%1 95 If transaminase 1.5 normal value or alkaline phosphatase 2.5 normal value to reduce the dose by 25% Do not administered if serum bilirubin increased or transaminase 3.5 normal value or alkali

15、ne phosphatase 6 normal value如果转氨酶 1.5正常值，或者碱性磷酸酶 2.5正常值，减少25%的剂量。如果血清胆红素升高或者转氨酶 3.5正常值，或者碱性磷酸酶 6正常值，则不给药。Dactinomycin 更生霉素4 Not known Biliar excretion: 50-90% 胆汁排泄: 50-90%0.7 Not calculable 不可计算Daunorubicin (9) 柔红霉素4 Not known Mainly liver: formation of a metaboli te with cytotoxic activity (daunor

16、ubicinol), glucuronide, sulfate and aglycones 主要经肝代谢：形成有细胞毒活性的代谢物（柔红霉素醇），葡糖苷酸，硫酸和苷元0.9 If total bilirubin 1.5-3 reduce 25%，If total bilirubin 3 reduce 50% 若总胆红素1.5-3，减少25%的剂量，若总胆红素3，减少50%的剂量Idarubicin (9) 伊达比星1 1 Extensive liver metabolism idarubicinol 广泛的肝代谢 伊达比星醇0.4 96 If total bilirubin=2.6-5 dos

17、e reduction 50%，Do not administer if total bilirubin 5 mg/dL 如果总胆红素=2.6-5，减少50%剂量，如果总胆红素5mg/dL,不能给予Ifosfamide* (9) 异环磷酰胺3 0.02 Liver metabolism: CYP3A 肝脏代谢：CYP3A0.5 Monitor liver function 监测肝功能Mitomycin Prod Info Mitomycin-C, 2007 (27) 丝裂霉素4 Not known Partial liver metabolism 部分肝代谢0.9 Avoid 避免使用Mito

18、xantrone* Prod Info Novantrone, 2007 (27) 米托恩醌2 0.47 Biliar excretion: 25% 胆汁排泄：25%0.95 76 Adjust dose at 8 mg/m2 or avoided in patients with total bilirubin 3.5 mg/dL or acute liver dysfunction 调整剂量到8 mg/m2或者避免用于总血红素 3.5 mg/dL或急性肝功能不全病人 Raltitrexed Prod Info Tomudex, 2002 (27) 雷替曲塞4 Not known Intra

19、cellular metabolism (polyglutamation) 细胞内代谢（聚谷氨酸化）0.5 93 Precaution 慎用Temozolomide Prod Info Temodal, 2009 (27) 替莫唑胺4 Not known 0.9 15 Precaution in Child-Pugh index 10 CPT评分 10，慎用Thiotepa* (9) 塞替派3 0.11 Extensive liver metabolism: triethylene phosphoramide active metabolite (TEPA) 广泛的肝代谢：三乙膦酰胺活性代谢物

20、(TEPA)0.5 99 Avoid in decompensated IH 避免用于失偿期IH用药Topotecan* Prod Info Hycamtin, 2007 (27) 拓扑替康2 0.33 Hydrolysis Biliar excretion: 20%水解胆汁排泄：20%0.6 35 No adjustment required 不需要调整Rituximab Prod Info Mabthera, 2010 (27) 利妥昔单抗4 Not known Monitor liver function, especially if the HI is due to HBV 监测肝功能

21、，特别是HBV导致的肝脏损伤Trastuzumab 曲妥单抗4 Not known 0.04 Not calculable 无法计算Sunitinib* Prod Info Sutent, 2007 (27) 舒尼替尼2 0.37 Liver metabolism: CYP3A4 肝代谢：CYP3A40.7 40-60 Child-Pugh A and B index: adjustment not required Child-Pugh C index. Monitor liver function CPT A，B：不需要调整CPT C：监测肝功能Sorafenib (9) 索拉非尼4 No

22、t known Liver metabolism: oxidation (CYP3A4) and glucuronidation (UGT1A9) 肝代谢: 氧化作用(CYP3A4)和糖脂化(UGT1A9) 0.8 24-48 Child-PughTotal bilirubinDose indexA1-1.5 Nv400 mg/12hB1.5-3 Nv200 mg/12hC 3 Nv200 mg/72hCPT总血红素用药剂量A1-1.5 Nv400 mg/12hB1.5-3 Nv200 mg/12hC 3 Nv200 mg/72hNv: normal value Reduced 50% decrease in cholinesterase levels. Monitor effect在胆碱酯酶下降患者中减少50%剂量，监测效应ImatinibProd Info Gleevec, 2008 (27) 伊马替尼4 Not known N-demethylation: CYP 3A Biliar excretion: 20% N-脱甲基作用：CYP 3A胆汁排泄：20%0.95 95 In patients Child-Pugh C index reduce doses to 25%。Do not administer if total bilirubin