CINV化療相關(guān)嘔吐

1、1會(huì)計(jì)學(xué)CINV化療相關(guān)嘔吐化療相關(guān)嘔吐2235-HT3=5羥色胺受體類型3; NK1=神經(jīng)激肽 1.吩噻嗪 (多巴胺)地塞米松大劑量胃復(fù)安 (羥色胺)聯(lián)合療法確定預(yù)測(cè)變量首個(gè)5-HT3受體拮抗劑進(jìn)一步了解遲發(fā)性嘔吐地塞米松和5-HT3受體拮抗劑聯(lián)合療法首個(gè)NK1受體拮抗劑(P物質(zhì))1960s1970s1980s1990s2000s345腦干嘔吐中樞1,2 最后區(qū) 化學(xué)受體激發(fā)區(qū)(CTZ) 孤束核 迷走神經(jīng)運(yùn)動(dòng)背核 P物質(zhì)/神經(jīng)激肽 1 (NK1)受體1 羥色胺/5-HT3受體1GI 迷走神經(jīng)傳入神經(jīng)纖維1羥色胺/5-HT3受體P物質(zhì)/NK1受體1. Hesketh PJ et al. Eur

2、 J Cancer. 2003;39(8):10741080.2. Grunberg SM，Hesketh PJ. N Engl J Med. 1993;329(24):17901796.Illustration by Kirk Moldoff.56化療細(xì)胞損傷CTZ 活化活化嘔吐中樞增加傳出輸入至靶器官導(dǎo)致嘔吐增加傳入輸入至CTZ和嘔吐中樞 血液 腦脊液1. Hesketh PJ，Blanchard EM. In: DeVita VT Jr et al. 8th ed. Cancer: Principles & Practice of Oncology. Lippincott Wil

3、liams & Wilkins; 2008:26392646.Illustration by Kirk Moldoff. 神經(jīng)活性劑的釋放 迷走神經(jīng)活化671. Hesketh PJ，Blanchard EM. In: DeVita VT Jr et al. 8th ed. Cancer: Principles & Practice of Oncology. Lippincott Williams & Wilkins; 2008:26392646.78嘔吐反射羥色胺P物質(zhì)阿片類多巴胺組胺乙酰膽堿1. Hesketh PJ et al. Eur J Cancer. 200

4、3;39(8):10741080.89CINV羥色胺P物質(zhì)1. Hesketh PJ et al. Eur J Cancer. 2003;39(8):10741080.9101. Miner WD，Sanger GJ. Br J Pharmacol.1986;88:497499.2. Hesketh PJ et al. Eur J Cancer.2003;39(8):10741080.10111. DeVane CL. Pharmac其他apy. 2001;21(9):10611069.2. Hargreaves R. J Clin Psychiatry. 2002;63(suppl 11):

5、1824.3. Hesketh PJ et al. Eur J Cancer. 2003;39(8):10741080.4. Hesketh PJ. Support Care Cancer. 2001;9(5):350354.11121358%0% 10% 20% 30% 40% 50% 60% 70%發(fā)生CINV患者比例中致吐性化療止吐療法第1天:昂丹司瓊 (8 mg P.O. bid) and地塞米松 (20 mg P.O.)第2 & 3天: 昂丹司瓊 (8 mg P.O. bid)P.O.=口服; bid=每日2次.A定義為完全應(yīng)答（無(wú)嘔吐和使用挽救藥物） 1. Warr DG

6、et al. J Clin Oncol. 2005;23:28222830.盡管使用了5-HT3受體拮抗劑和皮質(zhì)類固醇，臨床試驗(yàn)顯示患者仍會(huì)發(fā)生CINV。a第 15天131448%0% 10% 20% 30% 40% 50% 60% 70%發(fā)生CINV患者比例高致吐性化療P.O.=口服; bid=每日2次; I.V.=靜脈注射. A定義為完全應(yīng)答（無(wú)嘔吐和使用挽救藥物） 1. Warr DG et al. J Clin Oncol. 2005;23:28222830.第 15天14盡管使用了5-HT3受體拮抗劑和皮質(zhì)類固醇，臨床試驗(yàn)顯示患者仍會(huì)發(fā)生CINV。a止吐療法第1天: 昂丹司瓊 (32

7、 mg I.V.) and地塞米松 (20 mg P.O.)第2-4天: 昂丹司瓊 (8 mg P.O. bid)151. Lau PM et al. Support Care Cancer. 2004;12(9):626633.2. Kris MG et al. J Clin Oncol. 2006;24(33):29322947.3. Osoba D et al. Support Care Cancer. 1997;5(4):307313.4. Aapro MS et al. Support Care Cancer. 2005;13(2):117121.1516癌癥類型/化療方案臨床試驗(yàn)中

8、報(bào)告的CINV比例% ，按級(jí)別級(jí)別1級(jí)別2級(jí)別3級(jí)別4所有級(jí)別乳腺癌蒽環(huán)類+環(huán)磷酰胺 (AC)1惡心: 43嘔吐: 21321675118242卵巢癌順鉑+紫杉醇2NV: 344017-91腹腔順鉑3NV: 8282肺癌順鉑+培美曲塞458226-NV: 86NV=惡心 和 嘔吐.1. Jones SE et al. J Clin Oncol. 2006;24:53815387. 2. Neijt JP et al. J Clin Oncol. 2000;18(17):30843092. 3. Piccart MJ et al. Int J Gynecol Cancer. 2003;13(su

9、ppl 2):196203. 4. Manegold C et al. Ann Oncol. 2000;11:435-4401617癌癥類型/化療方案臨床試驗(yàn)中報(bào)告的CINV比例% ，按級(jí)別級(jí)別1級(jí)別2級(jí)別3級(jí)別4所有級(jí)別乳腺癌多西紫杉醇+環(huán)磷酰胺 (TC)1惡心: 38嘔吐: 913521170 mg/m2 的化療方案 (平均順鉑劑量=80 mg/m2)阿瑞吡坦組(n=260)活性對(duì)照組(n=261) 一項(xiàng)隨機(jī)、平行、多中心、雙盲對(duì)照試驗(yàn)。 第二個(gè)研究的設(shè)計(jì)與研究1相同（共569名患者）。2331. Hesketh PJ et al. J Clin Oncol. 2003;21(22):41

10、124119.2. Poli-Bigelli S et al. Cancer. 2003;97(12):30903098.高致吐性化療34阿瑞吡坦方案阿瑞吡坦125 mg P.O.阿瑞吡坦80 mg P.O. qd地塞米松12 mg P.O.地塞米松8 mg P.O. (AM)昂丹司瓊32 mg I.V.活性對(duì)照方案地塞米松20 mg P.O.地塞米松8 mg P.O. (AM/PM)昂丹司瓊32 mg I.V.第1天第2天第3天阿瑞吡坦地塞米松昂丹司瓊第4天I.V.=靜脈注射; P.O.=口服; qd=每天1次.阿瑞吡坦和地塞米松的安慰劑被用于維持盲態(tài)。 341. Hesketh PJ et

11、 al. J Clin Oncol. 2003;21(22):41124119.2. Poli-Bigelli S et al. Cancer. 2003;97(12):30903098.高致吐性化療35n高致吐性化療351. Gralla RJ et al. Cancer. 2005;104:864868.36第 15 天阿瑞吡坦組 (n=260)活性對(duì)照組 (n=261)完全應(yīng)答:無(wú)嘔吐事件，未使用針對(duì)惡心或嘔吐的挽救藥物完全應(yīng)答患者比例，%研究1，周期1，各治療組中患者應(yīng)答情況P0.001 在研究2中，阿瑞吡坦治療組和活性對(duì)照組中完全應(yīng)答患者比例和研究1類似 (63% vs 43%，P0

12、.001).2361. Hesketh PJ et al. J Clin Oncol. 2003;21(22):41124119.2. Poli-Bigelli S et al. Cancer. 2003;97(12):30903098.高致吐性化療研究1，周期1，各治療組中患者應(yīng)答情況37*P0.001 研究1和2中Log-rank檢驗(yàn)，名義p值未進(jìn)行多重調(diào)整 研究2顯示類似結(jié)果。2371. Hesketh PJ et al. J Clin Oncol. 2003;21(22):41124119.2. Poli-Bigelli S et al. Cancer. 2003;97(12):309

13、03098.高致吐性化療研究1，周期1，無(wú)嘔吐患者比例 阿瑞吡坦組 (n=260) 活性對(duì)照組 (n=261)患者%小時(shí)38020406080100周期2周期3周期 4周期 5周期 6阿瑞吡坦組4637221411活性對(duì)照組382515117完全應(yīng)答=無(wú)嘔吐事件，未因惡心和嘔吐使用挽救性治療.阿瑞吡坦組活性對(duì)照組 研究2顯示類似結(jié)果。2完全應(yīng)答患者比例，%381. De Wit R et al. J Clin Oncol. 2003;21(22):41054111.2. De Wit R et al. Eur J Cancer. 2004;40:403410.高致吐性化療39aFLIE=日常生

14、活功能指數(shù)嘔吐.391. Hesketh PJ et al. J Clin Oncol. 2003;21(22):41124119.2. Poli-Bigelli S et al. Cancer. 2003;97(12):30903098.高致吐性化療40不良事件阿瑞吡坦組，%(n=544)活性對(duì)照組，%(n=550)乏力/疲勞1812惡心1312打嗝116便秘1012腹瀉107厭食109401. Warr DG et al. Eur J Cancer. 2005;14:12781285.2個(gè)關(guān)鍵3期臨床試驗(yàn)的匯總數(shù)據(jù)4142接受含環(huán)磷酰胺和阿霉素/表阿霉素 化療方案的乳腺癌患者阿瑞吡坦組(n

15、=438)對(duì)照方案(n=428) 一項(xiàng)隨機(jī)、平行、多中心、雙盲對(duì)照試驗(yàn)421. Warr DG et al. J Clin Oncol. 2005;23:28222830.中致吐性化療43阿瑞吡坦方案阿瑞吡坦125 mg P.O.阿瑞吡坦80 mg P.O. qd地塞米松12 mg P.O.昂丹司瓊8 mg P.O. bid對(duì)照方案地塞米松20 mg P.O.昂丹司瓊8 mg P.O.bid昂丹司瓊8 mg P.O. bid第1天第2天第3天阿瑞吡坦地塞米松昂丹司瓊I.V.=靜脈注射; P.O.=口服; qd=每日1次; bid=每日2次. 阿瑞吡坦和地塞米松的安慰劑被用于維持盲態(tài)。 431.

16、 Warr DG et al. J Clin Oncol. 2005;23:28222830.中致吐性化療 治療組間的差異主要由“無(wú)嘔吐”終點(diǎn)來(lái)決定，這是復(fù)合首要研究終點(diǎn)的最重要組成部分。441. Warr DG et al. J Clin Oncol. 2005;23:28222830.中致吐性化療第15天阿瑞吡坦組 (n=433)對(duì)照組(n=424) 完全應(yīng)答患者比例，%對(duì)治療組應(yīng)答的患者，周期 1P=0.015完全應(yīng)答:無(wú)嘔吐事件，未使用針對(duì)惡心或嘔吐的挽救藥物5154545542393938020406080100周期 1周期 2周期 3周期 4完全應(yīng)答的概率%阿瑞吡坦組對(duì)照組a 全部

17、4個(gè)周期內(nèi)阿瑞吡坦組患者持續(xù)CR的累計(jì)比例顯著更高 (P=0.017).1. Herrstedt J et al. Cancer. 2005;104:15481555.2. Warr DG et al. J Clin Oncol. 2005;23:28222830.45Reprinted with permission from John Wiley & Sons，Inc.: Cancer. 2005;104:1548-1555.中致吐性化療4646中致吐性化療不良事件阿瑞吡坦組，%(n=438)對(duì)照組，% (n=428)脫發(fā)2422.2疲勞21.921.5頭痛16.416.4便秘12

18、.318中性粒細(xì)胞減少8.98.4消化不良8.44.9口腔炎5.34.4咽喉疼痛32.3潮熱 31.4與區(qū)域說(shuō)明書(shū)一致 47阿瑞吡坦組(n=430)對(duì)照組(n=418) 3期、隨機(jī)、按性別分層、雙盲試驗(yàn)上市后研究1. Rapoport B et al. Support Care Cancer. 2010;18:423431.47中致吐性化療48阿瑞吡坦組阿瑞吡坦125 mg P.O.阿瑞吡坦80 mg P.O. qd地塞米松12 mg P.O.昂丹司瓊8 mg P.O. bid對(duì)照方案地塞米松20 mg P.O.昂丹司瓊8 mg P.O. bid昂丹司瓊8 mg bid第1天第2天第3天P.O

19、.=口服; qd=每日1次; bid=每日2次.1. Rapoport B et al. Support Care Cancer. 2010;18:423431.48中致吐性化療49阿瑞吡坦組(n=430)對(duì)照組(n=418)女性男性76.024.077.822.2年齡，y 平均值 (SD)57.1 (11.8)55.9 (12.6)主要診斷，% 乳腺癌 大腸癌 肺癌 卵巢癌50.120.011.85.852.620.013.33.3化療方案，% 非-AC AC53.546.551.248.8暈車史，%5.69.8孕期嘔吐史,%14.217.9AC=蒽環(huán)類+環(huán)磷酰胺; SD=標(biāo)準(zhǔn)差.1. Ra

20、poport B et al. Support Care Cancer. 2010;18:423431.49中致吐性化療5062760102030405060708090系列1第 15天 (0120小時(shí))阿瑞吡坦組(n=425)對(duì)照組(n=407)無(wú)嘔吐: 無(wú)嘔吐或干嘔無(wú) 嘔吐患者比例，% 和對(duì)照組相比，接受含阿瑞吡坦方案的患者在5天內(nèi)無(wú)嘔吐的比例顯著更高。P0.0011. Rapoport B et al. Support Care Cancer. 2010;18:423431.50中致吐性化療51566901020304050607080系列1完全應(yīng)答:無(wú)嘔吐，未使用挽救性藥物完全應(yīng)答患者

21、比例，%P0.0011. Rapoport B et al. Support Care Cancer. 2010;18:423431.51阿瑞吡坦組(n=425)對(duì)照組(n=407)中致吐性化療第 15天 (0120小時(shí)) 和對(duì)照組相比，接受含阿瑞吡坦方案的患者在5天內(nèi)完全應(yīng)答的比例顯著更高。52AC=蒽環(huán)類+環(huán)磷酰胺.1. Rapoport B et al. Support Care Cancer. 2010;18:423431.53716883020406080100AC (n=403)非-AC (n=429)患者患者%對(duì)照組阿瑞吡坦組 vs 對(duì)照15%12%52P0.05P0.05中致吐

22、性化療53AC=蒽環(huán)類+環(huán)磷酰胺.1. Rapoport B et al. Support Care Cancer. 2010;18:423431.53P0.05PNS中致吐性化療47666374020406080100AC (n=403)非-AC (n=429)患者患者%對(duì)照組阿瑞吡坦組 vs 對(duì)照16%8%54不良事件阿瑞吡坦組，% (n=430)對(duì)照方案，%(n=418)疲勞10.99.8頭痛10.012.2腹瀉9.811.2便秘8.613.4厭食8.18.9脫發(fā)6.57.7乏力6.35.51. Rapoport B et al. Support Care Cancer. 2010;18

23、:423431.54中致吐性化療552 個(gè)關(guān)鍵路徑，2種關(guān)鍵神經(jīng)遞質(zhì)1. Hesketh PJ et al. Eur J Cancer. 2003;39:10741080. Illustration by Kirk Moldoff.中樞路徑 由P物質(zhì)活化 主要由神經(jīng)激肽 1 (NK1)受體介導(dǎo)，高度集中在腦部 由羥色胺刺激 由5-HT3受體介導(dǎo)，主要位于腸道 外周路徑56570123456789404812 16 20 24 28 32 36 40 44 485-HIAA:肌酐比值順鉑給藥后時(shí)間1. Wilder-Smith OHG et al. Cancer. 1993;72:2239224

24、1.575-HIAA=5-羥吲哚乙酸.Reprinted with permission from John Wiley & Sons，Inc.: Cancer. 1993;72:22392241.580123456789404812 16 20 24 28 32 36 40 44 485-HIAA:肌酐比值順鉑給藥后時(shí)間1. Wilder-Smith OHG et al. Cancer. 1993;72:22392241.58Reprinted with permission from John Wiley & Sons，Inc.: Cancer. 1993;72:22392

25、241.5-HIAA=5-羥吲哚乙酸.16-48小時(shí)在前順鉑水平的5-HT3 標(biāo)記物5-HIAA帕洛諾司瓊格拉司瓊昂丹司瓊多拉司瓊5940.725.2020406080100帕洛諾司瓊 (n=150)完全應(yīng)答患者比例%高致吐性化療1,a69.350.3020406080100帕洛諾司瓊 (n=189)完全應(yīng)答患者比例%中致吐性化療34634020406080100帕洛諾司瓊 (n=189)完全應(yīng)答患者比例%中致吐性化療3601. Aapro MS et al. Ann Oncol. 2006;17:14411449. 2. Gralla R. Ann Oncol. 2003;14:157015

26、77. 3. Eisenberg P et al. Cancer. 2003;98:24732482. P0.025P=0.021P0.0001a 結(jié)果來(lái)源于接受5-HT3 拮抗劑+地塞米松治療的子集611. Hesketh PJ et al. Support Care Cancer. 2011;19(9):12971302.61來(lái)源于2個(gè)3期臨床試驗(yàn)的數(shù)據(jù)研究了進(jìn)行高致吐性化療患者在不同時(shí)間段內(nèi)發(fā)生首次嘔吐的比例?；颊唠S機(jī)分入止吐方案：阿瑞吡坦+昂丹司瓊+地塞米松 或 昂丹司瓊+地塞米松。141210864200102030405060701001108090昂丹司瓊+地塞米松阿瑞吡坦+昂丹

27、司瓊+地塞米松發(fā)生首次嘔吐的患者比例,%化療后時(shí)間，小時(shí)Support Care Cancer，19(9)，2011，12971302. Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chem其他apy (HEC and MEC)，Hesketh PJ et al，F(xiàn)igure 1， Springer-Verlag 2011. With permission of Springer Science+B

28、usiness Media.626363的患者比例1. Longo F et al. Support Care Cancer. 2011;19(8):11591164.64阿瑞吡坦125 mg P.O.80 mg P.O. qd帕洛諾司瓊0.25 mg I.V.地塞米松20 mg I.V.4 mg P.O. 或 I.M. qda第1天第2天第3天a與阿瑞吡坦聯(lián)合使用第2和3天的地塞米松劑量低于常規(guī)推薦8 mg/天的劑量。 P.O.=口服; I.V.=靜脈注射; qd=每日1次; I.M.=肌肉注射.1. Longo F et al. Support Care Cancer. 2011;19(8

29、):11591164.65性別76.6% 男性中位年齡，y 62順鉑劑量，% 80 mg/m2 75 mg/m2 70 mg/m213.054.532.5癌癥診斷，% 肺 頭頸 胃 其他66.71. Longo F et al. Support Care Cancer. 2011;19(8):11591164.661. Longo F et al. Support Care Cancer. 2011;19(8):11591164.97.772.570.3020406080100急性期（第1天）遲發(fā)期（第2-5天）全階段（第1-5天）完全應(yīng)答患者比例%671. Longo F

30、 et al. Support Care Cancer. 2011;19(8):11591164.97.79592.8020406080100急性期（第1天）遲發(fā)期（第2-5天）全階段（第1-5天）無(wú)嘔吐患者比例%68a 允許瀉藥治療1. Longo F et al. Support Care Cancer. 2011;19(8):11591164.697070n1. Grote T et al. J Support Oncol. 2006;4(8):403408.71阿瑞吡坦125 mg P.O.80 mg P.O. qd帕洛諾司瓊0.25 mg I.V.地塞米松12 mg P.O.8 mg

31、 P.O. qd第1天第2天第3天P.O.=口服; I.V.=靜脈注射; qd=每日1次.1. Grote T et al. J Support Oncol. 2006;4(8):403408.72性別78% 女性中位年齡,歲(范圍)59.5 (3584)種族，% 白人 西班牙裔美國(guó)人 非洲裔美國(guó)人 其他711478癌癥診斷，% 乳腺癌 大腸癌 淋巴瘤 肺癌 其他47141212151. Grote T et al. J Support Oncol. 2006;4(8):403408.This article was published in J Support Oncol，4(8)，Grot

32、e et al，Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron，dexamethasone，and aprepitant，403408，Copyright Elsevier (2006).731. Grote T et al. J Support Oncol. 2006;4(8):403408.主要化療藥物，% 環(huán)磷酰胺 (1500 mg/m2) 蒽環(huán)類 卡鉑 奧沙利鉑51

33、.739.725.910.3化療方案，% 含蒽環(huán)類/環(huán)磷酰胺 含卡鉑/紫杉醇 含奧沙利鉑41.422.410.3既往化療，%55741. Grote T et al. J Support Oncol. 2006;4(8):403408.887878020406080100急性期（第1天）遲發(fā)期（第2-5天）全階段（第1-5天）完全應(yīng)答患者比例%75751. Grote T et al. J Support Oncol. 2006;4(8):403408.939391020406080100急性期（第1天）遲發(fā)期（第2-5天）全階段（第1-5天）無(wú)嘔吐患者比例%76便秘21腹瀉17疲乏16失眠1

34、4血小板減少癥101. Grote T et al. J Support Oncol. 2006;4(8):403408.7677a 由研究者評(píng)定為可能、很可能或肯定和研究藥物有關(guān)。1. Grote T et al. J Support Oncol. 2006;4(8):403408.781. Rojas C et al. Anesth Analg. 2008;107:469478. 2. Aapro MS et al. Ann Oncol. 2006;17:14411449. 3. Gralla R. Ann Oncol. 2003;14:15701577. 4. Eisenberg P e

35、t al. Cancer. 2003;98:24732482. 5. Wilder-Smith OHG et al. Cancer. 1993;72:22392241. 6. Hesketh PJ et al. Support Care Cancer. 2011;19(8):12971302. 7. Aloxi (帕洛諾司瓊). Summary of Product Characteristics. March 2010. 8. Longo F et al. Support Care Cancer. 2011;19(8):11591164. 9. Grote T et al. J Suppor

36、t Oncol. 2006;4(8):403408.78核對(duì)當(dāng)?shù)嘏谅逯Z司瓊的適應(yīng)癥791. Majem M et al. Published online ahead of print 18 November 2010. Support Care Cancer. doi:10.1007/s00520-010-104.HCP=衛(wèi)生保健專家 7997.610010090.69196.5020406080100順鉑 高致吐性化療 阿瑞吡坦+格拉司瓊+地塞米松中致吐性化療 格拉司瓊+地塞米松無(wú)嘔吐患者比例，%患者報(bào)告HCP預(yù)測(cè)801. Majem M et al. Published online a

37、head of print 18 November 2010. Support Care Cancer. doi:10.1007/s00520-010-104.HCP=衛(wèi)生保健專家 8181HCP=衛(wèi)生保健專家.1. Majem M et al. Published online ahead of print 18 November 2010. Support Care Cancer. doi:10.1007/s00520-010-104.92.96077.888.690.896.2020406080100順鉑 高致吐性化療 阿瑞吡坦+格拉司瓊+地塞米松中致吐性化療 格拉司瓊+地塞米松無(wú)嘔吐患

38、者比例，%患者報(bào)告HCP預(yù)測(cè)8282HCP=衛(wèi)生保健專家.1. Majem M et al. Published online ahead of print 18 November 2010. Support Care Cancer. doi:10.1007/s00520-010-104.83適當(dāng)?shù)某杀?效益數(shù)據(jù)必須由當(dāng)?shù)蒯t(yī)學(xué)/法務(wù)決定848585德國(guó)1高致吐性化療0.001721%28,891比利時(shí)2高致吐性化療0.0032.2%占優(yōu)勢(shì)a中致吐性化療0.01412%占優(yōu)勢(shì)aQALY=質(zhì)量調(diào)整生命年; ICER=增量成本-效益比 (增量成本/增量效益). a ICER占優(yōu)勢(shì)意味著QALY增加，

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46、upport Care Cancer. 2010;18:423431.7. Herrstedt J et al. Cancer. 2005;104(7):15481555.98981. Grunberg S et al. J Clin Oncol. 2011;29(11):14951501.991. Kris MG et al. J Clin Oncol. 2006;24(33):29322947.2. NCCN Clinical Practice Guidelines in Oncology: Anti嘔吐V1.2012. National Comprehensive Cancer Netw

47、ork. /professionals/physician_gls/f_guidelines.asp. Accessed 10 August 2011.3. Roila F et al. Ann Oncol. 2010;21(suppl 5):v232v243. 4. Eaton LH，Tipton JM. 化療-induced 惡心 and 嘔吐. In: Putting Evidence Into Practice: Improving Oncology Patient Outcomes. Pittsburgh，PA: Oncology Nursing Society; 2

48、009:6383. 991001. NCCN Clinical Practice Guidelines in Oncology: Anti嘔吐V1.2012. National Comprehensive Cancer Network. /professionals/physician_gls/f_guidelines.asp. Accessed 10 August 2011.100I.V.=靜脈注射.101具體內(nèi)容參照后面片子格式，詳細(xì)信息參見(jiàn)中文版說(shuō)明書(shū)。不要所有EMEND IV 內(nèi)容。102Align with local label103，. Inhibition of

49、 CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs，potentially causing serious or life-threatening reactions.Align with local label104Align with local label105and for 28 days after the last dose of EMEND. Alternative or backup methods of contraception should be used during treatment with EMEND and for 1 month after the last dose of EMEND.Align with local lab