表柔比星膀胱内灌注化疗方案的优化课件

表柔比星膀胱内灌注方案的优化福建省立医院泌尿外科李涛Thereisnosingledrugthatissuperiorwithregardstoefficacy.MitomycinC,epirubicinanddoxorubicinhaveallshownabeneficialeffect(evidence:1b).2010EAU对NMIBC的治疗的推荐TURBT+即刻单次膀胱内灌注复发复发/进展根治性膀胱切除术化疗BCG+维持治疗单瘤、原发低分级Ta多发、复发低分级肿瘤任何T1和/或G3和/或原位癌观察复发/进展BCG+维持治疗低危中危高危TURBT+单次化疗TURBT+单次化疗表柔比星膀胱内灌注方案的优化剂量优化灌注频率和疗程的优化联合用药剂型优化比较法玛新不同剂量膀胱内灌注给药的研究

[50mg/50ml,80mg/50ml]Ali-El-DeinB,etal.TheJournalofUrology1997;158:68-74.膀胱内灌注在术后7-14天开始，每周进行一次，进行8周然后每月进行一次至一年疗程结束随访时间为12月-48月(平均为30.1月)组1：法玛新50mg/50ml生理盐水组2：法玛新80mg/50ml生理盐水组3：阿霉素50mg/50ml生理盐水组4：未接受任何辅助治疗浅表性膀胱癌患者R手术基线特征组1组2组3组4合计(%)分级pT1/pTa/Tis57/7/456/12/856/4/-55/6/-88.6/11.4/4.7分期I/II/III6/50/811/47/1010/42/812/40/915.4/70.8/13.8DNA双/四/异倍体48/8/850/14/440/12/845/13/372.3/18.6/19.1发病数单发/多发22/4228/4019/4119/4234.8/65.2肿瘤大小<3cm/3cm36/2846/2242/1845/1666.8/33.2Ali-El-DeinB,etal.TheJournalofUrology1997;158:68-74.研究结果：复发率Ali-El-DeinB,etal.TheJournalofUrology1997;158:68-74.平均随访30.1个月复发患者(%)(n=64)(n=68)(n=60)(n=61)组1-3vs.组4 p=0.0002组1-2vs.组3 p=0.02组1-2 p>0.05比较Ta/T1期移行细胞膀胱癌患者

接受TURBT术后两次法玛新膀胱内灌注研究SaikaT,etal.WorldJUrol2010.主要终点：至首次复发时间N=303A.TURBT+法玛新

20mg/40ml(N=79)TURBT术后1小时内即刻灌注1次，第二天早晨灌注1次，术后24小时内灌注2次C.仅TURBT(N=77)Ta/T1

移行细胞癌NMIBC患者B.TURBT+法玛新50mg/100ml

(N=84)TURBT术后1小时内即刻灌注1次，第二天早晨灌注1次，术后24小时内灌注2次R中位随访44个月研究结果：无复发生存SaikaT,etal.WorldJUrol2010.ABC中位RFS(月)243813时间(年)generalizedWilcoxontesBvs.C,P=0.041008060402000.01.02.03.04.05.0A法玛新20mg无复发率(%)B法玛新50mgC无法玛新比较高剂量法玛新膀胱内灌注与BCG

对中危浅表性膀胱癌患者预防作用的研究MoutzourisG,etal.EurUrolSuppl2007;6(2):171,Abstract595.DFS复发安全性N=234法玛新80mg/50ml生理盐水(N=121)BCG(N=113)TURBT术后原发或复发TaG2-3,T1G1-2TCC患者R每周膀胱内灌注，共六周；后续第3/6/12/18/24/30/36个月给予3次每周膀胱内灌注中位随访21个月前瞻性随机对照研究研究结果研究结论高剂量膀胱内灌注法玛新作为延长治疗方案耐受性良好对于中危NMIBC患者TURBT术后复发的预防疗效与BCG相同可评估患者法玛新(N=109)BCG(N=103)P肿瘤复发(%)31.220.40.1016中位DFS(月)23.2423.260.0778化学性膀胱炎(G1-G3)，%47.9354.870.1213因膀胱炎停药，%5.799.73-MoutzourisG,etal.EurUrolSuppl2007;6(2):171,Abstract595.表柔比星膀胱内灌注方案的优化剂量优化灌注频率和疗程的优化联合用药剂型优化HendricksenK,WitjesWP,IdemaJG,etal.EurUrol，2008，53(5)：984-991.

Patientswithintermediate-andhigh-riskurothelialcellcarcinomaofthebladder,exceptcarcinomainsitu,wererandomisedforadjuvantintravesicalinstillationswith50mgepirubicin/50mlNaClfor1h.Group1received4weeklyand5monthlyinstillations(standardschedule).group2receivedthesamescheduleasgroup1,butwithanadditionalinstillation<48hafterTURBT.group3receivedthesameschemeasgroup1,butwithadditionalinstillationsat9and12mo(maintenanceschedule).group1group2group35-yrrecurrencefree44.4%42.7%45.0%5-yrprogressionfree90.0%87.7%88.2%比较Ta/T1膀胱癌TUR术后

长疗程与短疗程法玛新膀胱内灌注的研究KogaH,etal.JUrol2004;171(1):153-157.N=150复发率安全性1年：法玛新30mg/30ml生理盐水×19(N=77)3个月：法玛新30mg/30ml生理盐水×9(N=73)TUR术后Ta/T1膀胱癌患者R膀胱内灌注次数1年组3个月组1TUR后<24小时2TUR后2-3天3TUR后1周4TUR后2周>55－10：每2周5－9：每2周11－19：每月－1年组3个月组5年RFS(％)85.263.9KogaH,etal.JUrol2004;171(1):153-157.研究结果：复发率术后时间(月)P=0.005无肿瘤复发患者比例(%)10080604020001224364860721年组3个月组表柔比星膀胱内灌注方案的优化剂量优化灌注频率和疗程的优化联合用药剂型优化RaitanenMP,LukkarinenO,FinnishMulticentreStudyGroup.

BrJUrol,1995,76(6):697-701.

Acontrolledstudyofintravesicalepirubicinwithorwithoutalpha2b-interferonasprophylaxisforrecurrentsuperficialtransitionalcellcarcinomaofthebladder.FinnishMulticentreStudyGroup.PATIENTSANDMETHODS:81patientswithsuperficial(stageTaandT1),wellormoderatelydifferentiated(grades1and2)TCCwererandomizedintothreegroups:Group1：TURalone;Group2：50mgepirubicin;Group3：50mgepirubicincombinedwith10MUalpha2b-IFN,intravesically.Theinstillationswerestarted1weekafterTURandwereperformedweeklyduringthefirstmonthandthenonceamonthforoneyear.RESULTS:Thepatientswerefollowedforameanof20months.Patientsreceivingintravesical

chemoimmunotherapy(Group3)hadthemostfavourableoutcome;theyhadcomparativelylowerrecurrenceandtumourrates,fewerpatientswithrecurrencesand,mostimportantly,thelongestdisease-freeinterval.Side-effectsweremostlymildandtransient,andnodifferenceswerefoundamongthegroups.NaitoS,etal.TheJournalofUrology，2008，179:485-490.LC：干酪乳酸菌多中心、前瞻性、随机对照研究临床诊断为浅表性膀胱癌患者TUR术后1周内膀胱内灌注(法玛新30mg/30ml生理盐水)共2次R法玛新组(N=102)术后3月内附加6次法玛新膀胱内灌注法玛新联合LC组(N=100)术后3月内附加6次法玛新膀胱内灌注口服干酪乳杆菌3mg/天持续1年评估复发、疾病进展、预后及药物不良反应基线特征NaitoS,etal.TheJournalofUrology2008;179:485-490.单药组联合组P总计1021000.2510性别(男/女)86/1678/22年龄

<70岁55530.8955≥70岁4747吸烟(是/否)53/4955/450.6650肿瘤类型原发单瘤40400.9903原发多瘤5250复发单瘤1010T分类(Ta/T1)53/4952/480.9955肿瘤分级(1/2)21/8121/790.9425肿瘤大小<1cm/≥1cm33/6931/690.8363研究结果：复发率单药组联合组中位随访(月)26.943.6复发率(%)41.226.03年RFS(%)59.974.6P=0.0234NaitoS,etal.TheJournalofUrology2008;179:485-490.100806040200012243648607284手术后时间(月)无复发生存率(%)单药组联合组GurtowskaN,KloskowskiT,DrewaT.

MedSciMonit,2010,16(10):218-223.

CiprofloxacincriteriainantimicrobialprophylaxisandbladdercancerrecurrenceAmongfluoroquinolones,ciprofloxacinisdistinguishedbystronginhibitionoftopoisomeraseII.Antiproliferativepotentialoftheciprofloxacinagainsthumanbladdercellsvariesaccordingtodrugconcentrationandtimeofincubation.LowurinepHcanenhancetheantitumoreffectofciprofloxacin.Ciprofloxacinenhancestheeffectofactionofdoxorubicinandepirubicin,whichareusedtopreventbladdercancerrecurrenceaftertransurethralresectionofsuperficialbladdercancer.Wethinkthatciprofloxacinmightbeusedforantibacterialprophylaxisandasananticanceragentinpatientswithsuperficialbladdercancer.

表柔比星膀胱内灌注方案的优化剂量优化灌注频率