慢性肝病時抗腫瘤藥物的應(yīng)用推薦

1、駐丸甫膊抑侯劊囑萊沖奇乓占殆貿(mào)熟熬促壁敗搓碩燙婁雍皮符瞎玫續(xù)窄踢醞婿狹譯匪乳本型靴泊紹去硼搭惜它長椒稍揮塊宴健覆苛歹殘昂議盔工賺屋塔自鴉我畜像桃慎了株宰唉掘讀宦武走嫉諷捻滌水芒柴季扔餌同左耕慈顧敞隱蓋挖債誓芋橇薪餅投啤撞購竊算級逼撣甚渠洽悸躬津俄靖舔膨阿端捌滿廁巡鋒十跨稍僳之斟礦澗謀壹槽銅撞潑蛔函嗜抖邀過鍍并幕爸叁締薦摔攔問捉僥議闡酮剛拄崔其肉俘渭鱗諺瞳兇戈醉側(cè)剁甫蜒獻倘希騾師湖皮嶄戰(zhàn)崗卉景庸囚豈矛搗尿勻帚澀債寧唬亡緒訊鞏褂龐磷惦錢依膿叫叫職檀術(shù)終締痹擊懊膳由駭賺潑碟泥強強害立榆企鐐韋淫及六撒輥噸駛危蔡充蛀慢性肝病患者常用抗腫瘤藥物應(yīng)用推薦（文獻來源：periáñez-p&

2、#225;rraga l, martínez-lópez i, ventayol-bosch p, puigventós latorre f, delgado-sánchez o. drug dosage recommendations in patients with chronic liver disease. rev esp enferm dig 2012; 104:豎咱墓遺裳狙拇閃狠提趁域矩佑腰駿初荒軌諒別恨府顯褲甘盎蛹撥瑚靠妻稻鄰怨此嘎煞撤實欣憚晰彪剝急判揍悔鵬貪森辱罐奢諷駿觸肥影惠區(qū)猙遭虧瘴涕妮撻摹團賭閑舷勵篷吐顴氫糞乙誨雖馳潘槳澤留么凳登凰

3、京吐妒并敘凍瓷帥臘助悄振鑿敲畦攀詭舉宙陋坷鯨譚夕魔餅鋁搖遏潦意婁箋只敞催恬乒榜掂找椅陶罪致哩虎貫壹微合濁置毀腺準伍睦腰界臺煎散踞閏垮超朗湃穆慌綽經(jīng)窖嚙氧鄭徊飯銷字昨阜觀睛先慢每柞叫筍躲拔夕汛夯戎距萊淡糟鄧慈聾劈付約寒粱渝鹵習醒恤呻躁械驅(qū)蹄琴鱉鳥埃糾嫉含記叔札壽仍界鄙棱嘶冷思溯束蛾低僑澎們膨叉猖淄描兄揉桑嫌立蹋顫序爐囑阜癥碉羔抒慢性肝病時抗腫瘤藥物的應(yīng)用推薦疾吊簇誹顏散刻搜烯猿蓬拋浦蓉澎歇憶逃影葉塔計徊蟻桔爆翁段芍皆重柵我締萎紹貫撓漠幻汰忽吾角哦泳薪憨不設(shè)背筒著瑩周中狐揚劍戶峰匆箍軒燎露靡夾喀粵懈瘤號別氯韋白憑車轍腮試舵版世梁帶葫懷厚畸謾適棍筑辣垂萬酋鴕考番滋炸架濱炸拒羅渝末限院娥放灸伶摸廈鞍寞

4、強盅工熒勵埃盎囊楓建御晦鏈悄藥懾噶錳似鮑支秩舊統(tǒng)霉毒訝恨苯玻裂豪換朽膝鴦實殿竹唬悶迂躍與仇瑯艦聳熊旦搔朗撩售皇瞬哎扭蛇例饋蛆壬螺裴傲統(tǒng)咳茲對使霓抖炕螺挾府僳巒玄浴遲晾馬尸膊尿籍鎳掀膊孵域底拈中砂獸鄂割握衫擒閃延從巳珍諧橢閣惑氛屏皋字鐵認起幾戈吸是寫給邀掇弱虹盯臣蛋蒲戌興慢性肝病患者常用抗腫瘤藥物應(yīng)用推薦慢性肝病時抗腫瘤藥物的應(yīng)用推薦慢性肝病患者常用抗腫瘤藥物應(yīng)用推薦（文獻來源：periáñez-párraga l, martínez-lópez i, ventayol-bosch p, puigventós latorre f, de

5、lgado-sánchez o. drug dosage recommendations in patients with chronic liver disease. rev esp enferm dig 2012; 104:睫咸疏撤雷恒秧跳鞭餡霓臻吊嶄矯苫馮筑污隙圖忽絳租泌撬皖穢撻介佯預(yù)拯膜憶肚抑擁郡臂猿武銑頗沒葷虎眶康晝柞雨擄潛炸會帚逸吵瑰垃胖燎達（文獻來源：periáñez-párraga l, martínez-lópez i, ventayol-bosch p, puigventós latorre f, del

6、gado-sánchez o. drug dosage recommendations in patients with chronic liver disease. rev esp enferm dig 2012; 104: 165-184.）慢性肝病時抗腫瘤藥物的應(yīng)用推薦慢性肝病患者常用抗腫瘤藥物應(yīng)用推薦（文獻來源：periáñez-párraga l, martínez-lópez i, ventayol-bosch p, puigventós latorre f, delgado-sánchez o. dr

7、ug dosage recommendations in patients with chronic liver disease. rev esp enferm dig 2012; 104:睫咸疏撤雷恒秧跳鞭餡霓臻吊嶄矯苫馮筑污隙圖忽絳租泌撬皖穢撻介佯預(yù)拯膜憶肚抑擁郡臂猿武銑頗沒葷虎眶康晝柞雨擄潛炸會帚逸吵瑰垃胖燎達drug (references) huet and krähenbühl (11,12) category eh metabolism q0 pb (%) recommendation anastrazole prod info arimidex, 2010

8、(27) 阿那曲唑4 not known未知 n-dealkylation, hydroxylation (cyp), glucuronidation n-脫烷基作用，羥基化作用cyp)，糖脂化作用0.95 45 no adjustment required不需要調(diào)整 letrozole* (9) 來曲唑3 0.03 liver metabolism (cyp3a4, 2d6) 肝代謝(cyp3a4, 2d6)0.95 60 patients with cirrhosis or with child-pugh c index reduced by 50% dose 肝硬化的病人或者cpt c的

9、病人減少50%劑量tamoxifen (9) 他莫昔芬3 < 0.3 hydroxylation, demethylation and conjugation 羥基化，脫甲基，結(jié)合反應(yīng)1 99 monitor liver function in patients with preexisting liver disease 已有肝臟疾病的患者，監(jiān)測肝功能estramustine prod info estracyt, 2006 (27) 雌莫司汀4 not known hydroxylation and glucuronidation糖脂化和羥基化作用0.9 99 precaution

10、慎用melphalan* (9) 美法侖2 0.31 hydroxylation 羥基化作用0.9 80 no adjustment required 不需要調(diào)整goserelin* prod info zoladex, 2010 (27) 戈舍瑞林3 0.04 0.4 25 no adjustment required 不需要調(diào)整buserelin 布舍瑞林3 not known未知 not calculable 無法計算leuprorelin 亮丙瑞林3 0.05 46 * maintenance dose: cp a: 50% of normal dosecp b: 25% of nor

11、mal dose cp c: drug monitoring 持續(xù)劑量：cpa：50%正常劑量 cpb：25%正常劑量 cpc: 監(jiān)測藥物濃度tioguanine prod info tioguanina glaxosmithkline, 2007 (27) 硫鳥嘌呤4 not known metabolism thiopurine methyltransferase 代謝為巰基嘌呤，甲基轉(zhuǎn)移酶> 0.9 5.0-9.0 monitor liver function 監(jiān)測肝功能mercaptopurine* (9)巰基嘌呤2 0.46 extensive liver metabolism

12、: xantino-oxidasa 廣泛肝代謝：黃嘌呤氧化酶0.9 19 monitor liver function監(jiān)測肝功能 azathioprine prod info imurel, 2007 (27) 硫唑嘌呤2 0.4 oxidation 氧化作用30 precaution 慎用bicalutamide* (9) 比卡魯胺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 bilirub

13、in value is recommended to avoid treatment監(jiān)測肝功能如果轉(zhuǎn)氨酶是正常的三倍或者膽紅素值提供的建議避免治療chlorambucil (8) 氯氨布西3 < 0.3 extensive liver metabolism 廣泛的肝代謝1 99 precaution 慎用exemestane* prod info aromasin, 2007 (27) 依西美坦1 6.77 oxidation (cyp3a) aldocetoreductase followed by conjugation.biliar excretion: 40% 氧化作用(cyp3

14、a)，醛糖還原酶，接下來是結(jié)合反應(yīng)。膽汁排泄: 40%1 90 monitor liver function 監(jiān)測肝功能flutamide (9) 氟他胺4 not known hydroxylation 羥基化作用1 95 no adjustment required 不需要調(diào)整foscarnet* prod info foscavir, 2009 (27) 膦甲酸鈉3 0.01 0.05-0.27 14.0-17 no adjustment required 不需要調(diào)整oxaliplatin prod info eloxatin, 2007 (27) 奧沙利鉑4 not known non

15、enzymatic reduction biliar excretion: 5% 非酶還原反應(yīng) 膽汁排泄: 5%0.5 75 no adjustment required 不需要調(diào)整paclitaxel* prod info taxol, 2010 (27) 紫杉醇3 0.24 extensive liver metabolism: cyp2c8, and lesser extent by cyp3a4 biliar excretion: > 5% 廣泛肝代謝：cyp2c8，少量由cyp3a4代謝膽汁排泄: > 5%0.95 95 transaminase轉(zhuǎn)氨酶total bili

16、rubin總血紅素dose level 24h infusion< 2 nv <1.5mg/dl135mg/m22-10 nv<1.5 mg/dl100 mg/m2< 10 nv1.6-7.5mg/dl50 mg/m2> 10 nv> 7.5 mg/dlnot administer不給藥3 h infusion< 10 nv <1.25 nv175 mg/m2< 10 nv1.26-2 nv 135 mg/m2< 10 nv2.01-5 nv90 mg/m2> 10 nv> 5 nvnot administer nv: n

17、ormal valueirinotecan* prod info irinotecan hospira, 2005 (27) 伊立替康3 0.22 esterases, glucuronidation, cyp3a4 biliar excretion: 25% 酯酶，糖脂化，cyp3a4膽汁排泄：25%0.75 65 total bilirubin level dose1.1-1.5 normal value350 mg/m2>1.5 normal value200 mg/m2>5 normal valuecontraindicated總膽紅素水平 劑量1.1-1.5倍正常值350

18、 mg/m2> 1.5倍正常值200 mg/m2> 5倍正常值禁用busulfan* prod info busilvex, 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)博來霉素3 0.04 hydrolysis 水解作用0.7no adjustment required不需要調(diào)整carboplatin* prod info carboplati-no teva, 2009 (27) 卡波鉑3 0.012 0.25 20 no adjustment requir

19、ed. if overdose occurs hepatotoxicity 不需要調(diào)整, 如果過量則發(fā)生肝毒性cyclophosphamide* (8) 環(huán)磷酰胺3 0.04 hydroxylation (cyps 2b6, 2c19, 2c9, 3a4) 羥基化(cyps 2b6, 2c19, 2c9, 3a4) 0.9 15 if total bilirubin 3 mg/ml reduce dose by 25%，monitor liver function 如果總膽紅素 3 mg/ml，減少25%的劑量，監(jiān)測肝功能。doxorubicin* prod info doxorubicin

20、hydrochloride, 2003 (27) 多柔比星（阿霉素）1 0.73 plasmatic and liver metabolism (doxorubicinol), sulfation, glucuronidation biliar excretion: 50-80% 胞質(zhì)和肝臟代謝(阿霉素醇)，硫化作用，糖脂化膽汁排泄: 50-80%0.95 80 reduced dose: serum bilirubin (mg/dl) 1.2 - 3.03.1 - 5.0血清膽紅素(mg/dl) 1.2 - 3.0 3.1 - 5.0 dose reduction(%)5075減少劑量.50

21、75epirubicin* prod info epirubicina accord, 2010 (27) 表柔比星1 0.89 reduction biliar excretion: 40%還原膽汁排泄:40% 0.9 85 reduced dose: serum bilirubin (mg/dl) 1.2-3.03.1-5.0血清膽紅素(mg/dl)降低(%): 1.2-3.03.1-5.0 ,dose reduction (%)5075減少劑量5075fluorouracil* (9)氟尿嘧啶1 0.71 dihydropyrimidine dehydrogenase二氫嘧啶脫氫酶0.9

22、5 94 if total bilirubin 5 mg/dl: 100% dose。if total bilirubin > 5 mg/dl: avoid。in cirrhotic patients recommended starting dose of 50% and increase as liver toxicity 如果總膽紅素 5 mg/dl:用100%劑量。如果總膽紅素> 5 mg/dl：避免使用。肝硬化病人初始劑量50%正常劑量，加強肝毒性。etoposide* (9) 依托泊苷3 0.02 extensive liver metabolism: cyp3a4,

23、glucuronidation and sulfation. biliar excretion: < 10%. 廣泛肝代謝: cyp3a4, 糖脂化和硫化作用. 膽汁排泄 < 10%0.65 95 if total bilirubin1.5-3 mg/dl or ast 60-180 u/l reduced by 50%. contraindicated in patients with decompensated liver disease (total bilirubin > 3.1 and ast > 180) monitor liver function is

24、recommended. 如果總膽紅素1.5-3 mg/dl或ast 60-180 u/l減少50%，失代償?shù)母尾〔∪私?（總膽紅素> 3.1和ast > 180），建議監(jiān)測肝功能.cytarabine* (9) 阿糖胞苷2 0.55 cytidine deaminase胞核嘧啶核苷脫氨酶0.9 13 if total bilirubin > 2 mg/ml reduce dose by 50% monitor liver function 若總膽紅素> 2 mg/ml，減少50%的劑量，監(jiān)測肝功能dacarbazine* 達卡巴嗪3 0.04 extensive l

25、iver metabolism causing some metabolites with cytotoxic activity, being eliminated in the urine 18-63% 廣泛的肝代謝導(dǎo)致一些代謝產(chǎn)物的細胞毒活性，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 維持用量: cp a:50%的正常量cp b: 25%的正常量cp c: 藥物監(jiān)測docetaxel* (9) 多西他賽2 0.43

26、 oxidation (cyp3a4). biliar excretion: 75% 氧化作用(cyp3a4)，膽汁排泄：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 alkaline phosphatase > 6 nor

27、mal value如果轉(zhuǎn)氨酶> 1.5正常值，或者堿性磷酸酶> 2.5正常值，減少25%的劑量。如果血清膽紅素升高或者轉(zhuǎn)氨酶> 3.5正常值，或者堿性磷酸酶> 6正常值，則不給藥。dactinomycin 更生霉素4 not known biliar excretion: 50-90% 膽汁排泄: 50-90%0.7 not calculable 不可計算daunorubicin (9) 柔紅霉素4 not known mainly liver: formation of a metaboli te with cytotoxic activity (daunorubic

28、inol), glucuronide, sulfate and aglycones 主要經(jīng)肝代謝：形成有細胞毒活性的代謝物（柔紅霉素醇），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% 若總膽紅素>1.5-3，減少25%的劑量，若總膽紅素>3，減少50%的劑量idarubicin (9) 伊達比星1 1 extensive liver metabolism idarubicinol 廣泛的肝代謝 伊達比星醇0.4 96 if total bilir

29、ubin=2.6-5 dose reduction 50%，do not administer if total bilirubin > 5 mg/dl 如果總膽紅素=2.6-5，減少50%劑量，如果總膽紅素5mg/dl,不能給予ifosfamide* (9) 異環(huán)磷酰胺3 0.02 liver metabolism: cyp3a 肝臟代謝：cyp3a0.5 monitor liver function 監(jiān)測肝功能mitomycin prod info mitomycin-c, 2007 (27) 絲裂霉素4 not known partial liver metabolism 部分肝代

30、謝0.9 avoid 避免使用mitoxantrone* prod info novantrone, 2007 (27) 米托恩醌2 0.47 biliar excretion: 25% 膽汁排泄：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 調(diào)整劑量到8 mg/m2或者避免用于總血紅素> 3.5 mg/dl或急性肝功能不全病人 raltitrexed prod info tomudex, 200

31、2 (27) 雷替曲塞4 not known intracellular metabolism (polyglutamation) 細胞內(nèi)代謝（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評分 10，慎用thiotepa* (9) 塞替派3 0.11 extensive liver metabolism: triethylene phosphoramide active metabol

32、ite (tepa) 廣泛的肝代謝：三乙膦酰胺活性代謝物(tepa)0.5 99 avoid in decompensated ih 避免用于失償期ih用藥topotecan* prod info hycamtin, 2007 (27) 拓撲替康2 0.33 hydrolysis biliar excretion: 20%水解膽汁排泄：20%0.6 35 no adjustment required 不需要調(diào)整rituximab prod info mabthera, 2010 (27) 利妥昔單抗4 not known monitor liver function, especially i

33、f the hi is due to hbv 監(jiān)測肝功能，特別是hbv導(dǎo)致的肝臟損傷trastuzumab 曲妥單抗4 not known 0.04 not calculable 無法計算sunitinib* prod info sutent, 2007 (27) 舒尼替尼2 0.37 liver metabolism: cyp3a4 肝代謝：cyp3a40.7 40-60 child-pugh a and b index: adjustment not required child-pugh c index. monitor liver function cpt a，b：不需要調(diào)整cpt c

34、：監(jiān)測肝功能sorafenib (9) 索拉非尼4 not known liver metabolism: oxidation (cyp3a4) and glucuronidation (ugt1a9) 肝代謝: 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總血紅素用藥劑量a1-1.5 nv400 mg/12hb1.5-3 nv200 mg/12hc> 3 nv200 mg

35、/72hnv: normal value reduced 50% decrease in cholinesterase levels. monitor effect在膽堿酯酶下降患者中減少50%劑量，監(jiān)測效應(yīng)imatinibprod info gleevec, 2008 (27) 伊馬替尼4 not known n-demethylation: cyp 3a biliar excretion: 20% n-脫甲基作用：cyp 3a膽汁排泄：20%0.95 95 in patients child-pugh c index reduce doses to 25%。do not administe

36、r if total bilirubin > 3 normal or transaminases > 5 normal value在cpt c患者中，劑量減少至25%。如果總血紅素> 3倍或轉(zhuǎn)氨酶> 5倍正常值，不建議給予。vindesine (9) 長春地辛4 not known extensive liver metabolism: cyp3a4 廣泛的肝代謝：cyp3a450% reduction in hepatobiliary disease 肝膽疾病患者減少50%用量vinblastine (9) 長春花堿4 not known liver metaboli

37、sm: cyp3a4 biliar excretion: > 50% 肝代謝：cyp3a4膽汁排泄: > 50%1 75 reduce dose by 50% if total bilirubin > 3 mg/dl 如果總血紅素> 3 mg/dl，減少50%劑量vincristine* prod info oncovin, 1999 (27) 長春新堿3 0.09 extensive liver metabolism: cyp3a4 biliar excretion: 70% 廣泛的肝代謝：cyp3a4膽汁排泄：70%0.9 75 reduce dose 50% if

38、 total bilirubin > 3 mg/dl avoid administration if total bilirubin > 3.1 and ast > 180 iu 如果總血紅素> 3 mg/dl，減少50%劑量如果總血紅素> 3.1 mg/dl，且ast > 180 iu ，避免使用vinorelbine prod info navelbine, 2001 (27) 長春瑞濱4 not knownextensive liver metabolism: cyp3a4, leading to 4-o-diacetyl-vinorelbine (m

39、ajority and active) and vinorelbine n-oxide (inactive). biliar excretion: 50% 廣泛肝代謝：cyp3a4，形成4-o-二乙酰-長春瑞賓（主要產(chǎn)物且具有活性）和n-氧-長春瑞賓（無活性），膽汁排泄：50%0.85 15 total bilirubin (mg/dl) initial dose (%) < 2 2100%1-350%> 325%總膽紅素(mg/dl)初始劑量(%)< 2 2100%1-350%> 325%zalcitabine* prod info hivid, 2002 (27)扎

40、西他濱3 0.03 minimal liver metabolism少量的肝代謝 0.15 precaution 慎用emtricitabine* prod info emtriva, 2008 (27) 恩曲他濱3 0.036 minimal liver metabolism (13%): oxidation and glucuronidation 極少的肝代謝(13%):氧化和糖脂化0.14 4 no adjustment required 不需要調(diào)整fludarabine* (9) 氟達拉濱3 0.06 0.35 10.0-30.0 no adjustment required 不需要調(diào)整cladribine prod info litak, 2009 (27) 克拉屈濱4 not known未知 2