单剂量重复多次盐酸司琼注射液预防化疗所致恶心呕吐临床观察

1123456[摘要]目的：观察单剂量和重复多次剂量盐酸帕洛诺司琼预防化疗所致恶心、呕吐的疗效和安全性。方法：患者随机进入单剂量组（A组，盐酸帕洛诺司琼0.25mgd1iv，化疗前使用）≤245）10101两组在急性期呕吐v80.9%,P=0.193组呕吐率明显高于（v。A、B两组对于急性、延迟期恶心R率方面无差异。帕诺司琼与地塞米松联合使用对急性、延迟期呕吐R率高于单独使用帕诺司琼（分别为85.7%v75.6%,P=0.01,78.6%v64.4%,P=0.012），联合用药对延迟期恶心率高于单药（47.1%v32.7%,P=0.0005。多次重复剂量盐酸帕洛诺司琼较单剂量盐酸帕洛诺司琼可以化提高疗病人延迟期的呕吐率。 盐酸帕洛诺司琼；地塞米松；化疗；恶心；呕CINV效果并未较单用地塞米松有显著的提高[3]。帕洛诺司琼是近年来发展起来的第二代2011.8开始了单剂量和重复多次剂量盐酸帕洛诺司琼注射液预防化疗所致恶心、呕吐的临床入选标准：可接受化疗的恶性肿瘤患者，病种不限；具体化疗方案不限，I组（高度致吐性化疗组：化疗药物中包括接受含顺铂≥50mg/m2的化疗方案、卡莫司汀>250mg/m2、环磷酰胺>1500mg/m2、氮烯咪胺、阿霉素>60mg/m2、表阿霉素>90mg/m2、IFO≥10g/㎡或AC方案进行化疗的患者。II组（中度致吐性化疗组：用含任何剂量的卡铂、柔红霉素、草汀≤250mg/m2、甲氨喋呤≥250mg/m2、环磷酰胺≤1500mg/m2、阿糖胞苷>200mg/m2、血总胆红素≤1.5×正常值上限(ULN)；AST、ALT≤2.5×ULN(或≤5×ULN若有肝转移)；Cr、BUN≤1.5×ULN；电解质和心电图基本正常，符合化疗的适应证；距末次化疗结束2周以上患者；24小时内使用过止吐药物或化疗前已出现呕吐者；肿瘤脑转移患者，有颅内高压所致5-HT3受体拮抗剂类止吐药过敏者；有化疗禁忌2周内参加过其它新药临床研究者。。20118月～2011111016833例，18～74岁(48岁)。Karnofsky6018例，7020例，8025例，9025例，10092919例,1615例，乳65试验药品帕洛诺司琼（江苏正大天晴药业股份有限公司，0.25mg/瓶地塞米松为市场d3、d5ivIB组中化疗时间≤24天无呕吐5IIA0.25mgd1iv，化疗前使用。IIB0.25mgd1、d3、d5ivIIB组中化疗时间≤245天的盐酸帕洛诺司琼不需统计学处 采用SPSS13.0软件包行c2检验。P<0.05为差异具有显著性1.单、多剂量呕吐控制的比较0-24小时2-7天0-7天P2.单、多剂量恶心控制的比较0-24小时2-7天0-7天P3.是否合并使用激素，呕吐控制的比较0-24小时2-7天0-7天P4.是否合并使用激素，恶心控制的比较0-24小时2-7天0-7天P不良反应至目前为止共报告18（17.8%）例不良事件，分别为便秘6（5.9%）例，头级，没有严重不良反应（3-4级）发生。其中6例（33.3%）被认为和研究药物有关。为非吲哚类三环骨架结构[10]5-HT3相比，其为变构性拮抗剂，具有新结合位点，[11-12]、多[13]、格拉司琼[14]CINV的疗效基本5-HT3CINV的疗效有明显升高，而不良反应的种类和CINV的常用药物，近来研究发现，帕洛诺0.25mgCINV的（A组）和重复剂量组（B组）没有差异（76.3％v80.9P=0.19，而在延迟性呕吐方面，BCRA组（76.9％v63.2P=0.0012。对于恶心控制方面，A、B两组在急CRCR率明显升高（85.7％v75.6％P=0.011，延迟期呕吐CR率亦取得了相似的结果（78.6％v64.4％P=0.012。帕诺司琼合并使用激素后，对急性恶心的CR率无明显影响（52.9％v48.1％P=0.28P=0.00053（3.0%）例。所有不良事件均为轻微不良反应（1-2级（3-4CINV是安全有效的，并且体现出相对单剂量帕诺司琼的CINV的疗效，但目前本研究入组病Bloechl-DaumB,DeusonRR,PanagiotisMetalDelayednauseaandvomitingcontinuetoreducepatients’qualityoflifealterhighlyandmoderatelyemetogenicchemotherapydespiteantiemetictreatment.JClinOncol200624:4472–4478,GrunbergSM,DeusonR,MavrosPetal。Incidenceofchemotherapy-inducednauseaandemesisaftermodernantiemetics:perceptionversusreality.Cancer2004100:2261–2268,GelingO,EichlerHG:Should5-hyroxytryptamine-3receptorantagonistsbeadministeredbeyond24hoursafterchemotherapytopreventdelayedmesis?Systematicre-evaluationofclinicalevidenceanddrugcostimplications.JClinOncol,200523:1289-1294,BotrelTE,ClarkOA,ClarkLetalEfficacyofpalonosetron(PAL)comparedtootherserotonininhibitors(5-HT(3)R)inpreventingchemotherapy-inducednauseaandvomiting(CINV)inpatientsreceivingmoderatelyorhighlyemetogenic(MoHE)treatment:systematicreviewandmeta-analysis.SupportCareCancer.2010MayBillioA,MorelloE,ClarkeMetal.Serotoninreceptorantagonistsforhighlyemetogenicchemotherapyinadults.CochraneDatabaseSystRev.2010Jan20;(1)ZHOULIKUN,JINGXIANG,BAYIetal.ASystematicReviewandMeta-AnalysisofIntravenousPalonosetroninthePreventionofChemotherapy-InducedNauseaandVomitinginAdults.TheOncologist.2011;16:207–216Eisenberg,F.R.MacKintosh,P.Ritchetal.Efficacy,safetyandpharmacokineticsofpalonosetroninpatientsreceivinghighlyemetogeniccisplatin-basedchemotherapy:adose-rangingclinicalstudy.AnnalsofOncology15:330–337,2004M.Maemondo,N.Masudaetal.AphaseIIstudyofpalonosetroncombinedwithdexamethasonetopreventnauseaandvomitinginducedbyhighlyemetogenicchemotherapy.AnnalsofOncology20:1860–1866,2009RoilaF,WarrD,Clarck-SnowRAetal.Delayedemesis:moderatelyemetogenicchemotherapy.SupportCareCancer2005,13:104-108.Rojas,Camilo,Stathis,etal.PalonosetronExhibitsUniqueMolecularInteractionswiththe5-HT3Receptor.Anesthesia&Analgesia.2008August,107(2):469-478M.S.Aapro,S.M.Grunberg,G.M.Manikhasetal.AphaseIII,double-blind,randomizedtrialofpalonosetroncomparedwithondansetroninpreventingchemotherapy-inducednauseaandvomitingfollowinghighlyemetogenicchemotherapy.AnnalsofOncology17:1441–1449,R.Gralla,M.Lichinitser,S.VanderVegtetal.Palonosetronimprovespreventionofchemotherapy-inducednauseaandvomitingfollowingmoderatelyemetogenicchemotherapy:resultsofadouble-blindrandomizedphaseIIItrialcomparingsingledosesofpalonosetronwithondansetron..AnnalsofOncology14:1570–1577,2003PeterEisenberg,JazminFigueroa-Vadillo,RosalioZamoraetal.ImprovedPreventionofModeratelyEmetogenicChemotherapy-InducedNauseaandVomitingwithPalonosetron,aPharmacologicallyNovel5-HT3ReceptorAntagonist.Cancer2003;98:2473-82ZhaocaiYu,WenchaoLiu,LingWangetal.Theefficacyandsafetyofpalonosetroncompared.withgranisetroninpreventinghighlyemetogenic.chemotherapy-inducedvomitingintheChinesecancerpatients:aphaseII,multicenter,randomized,double-blind,parallel,comparativeclinicaltrial.SupportCareCancer(2009)17:99–102CamiloRojas,YingLi,JieZhang,etal.Theantiemetic5-HT3receptorantagonistpalonosetroninhibitsSubstanceP-mediatedresponsesinvitroandinvi