表柔比星膀胱内灌注化疗方案的优化课件.ppt

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 表柔比星膀胱内灌注方案的优化 提高疗效 尤其是能否替代BCG 减少不良反应增加便利性 减少不必要的灌注次数 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 基线特征 Ali El DeinB etal TheJournalofUrology1997 158 68 74 研究结果 复发率 Ali El DeinB etal TheJournalofUrology1997 158 68 74 研究结果 不良反应 Ali El DeinB etal TheJournalofUrology1997 158 68 74 研究结论 法玛新的剂量和疗效正相关临床推荐TURBT术后可常规使用50mg法玛新 最高可以用到80mg法玛新局部刺激性小 严重不良反应少 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 基线特征 SaikaT etal WorldJUrol2010 研究结果 无复发生存 SaikaT etal WorldJUrol2010 研究结果 不良事件 研究结论 TURBT后24小时内给予膀胱内灌注两次法玛新50mg比两次灌注20mg可进一步延长复发时间 且副作用很小 所有不良反应均可逆 SaikaT etal WorldJUrol2010 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 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 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 2019 12 20 19 可编辑 T rkeriL Tan d rY al etal UrolInt 2010 85 3 261 5 Comparisonoftheefficacyofsingleordoubleintravesicalepirubicininstillationintheearlypostoperativeperiodtopreventrecurrencesinnon muscle invasiveurothelialcarcinomaofthebladder prospective randomizedmulticenterstudy primaryandsolitaryormultiple 3orless Ta grade2 3 orT1 grade1 2 tumorswereenrolled Atotalof299patientsfrom24institutionswererandomizedtoreceiveeitherasingledoseof100mgepirubicininstillationwithin6horasecond100mgepirubicininstillationduringthe12th 18thhoursafteracompleteTUR BT RESULTS Thefollow upanddisease freesurvivalperiodswere16 9monthsand16months respectively CONCLUSIONS Asecondintravesicalepirubicininstillationdidnotprovideanysignificantbenefit 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 KogaH etal JUrol2004 171 1 153 157 研究结果 复发率 研究结果 不良反应 研究结论 与短疗程法玛新膀胱内灌注相比 长疗程 1年 法玛新明显降低复发率 且不增加严重不良反应 KogaH etal JUrol2004 171 1 153 157 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 Patientsreceivingintravesicalchemoimmunotherapy Group3 hadthemostfavourableoutcome theyhadcomparativelylowerrecurrenceandtumourrates fewerpatientswithrecurrencesand mostimportantly thelongestdisease freeinterval Side effectsweremostlymildandtransient andnodifferenceswerefoundamongthegroups MalmstromP WiklundF DuchekM etal JournalofUrology 2008 179 4 sup1 587 ADJUVANTINTRAVESICALEPIRUBICINANDINTERFERON2bISCOMPARABLETOBCGFORTREATMENTOFT1TUMOURSOFTHEURINARYBLADDER ThefirstTURoftheT1tumourwasfollowedwithin4 6weeksbyasecond lookresectionincludingbladdermappingandresectionbiopsyoftheprostaticurethra TwoweekslaterpatientsreceivedaccordingtorandomisationscheduleeitherBCG Oncotice orthecombinationofepirubicin Farmorubicin50mg andInterferon 2b 100 000IU Bothregimensgivenasinductiontreatmentfor6weeksfollowedbymaintenancetherapyfor2years Themeandurationoffollow upispresently3 2 0 1 7 9 years NaitoS etal TheJournalofUrology 2008 179 485 490 LC 干酪乳酸菌 基线特征 NaitoS etal TheJournalofUrology2008 179 485 490 研究结果 复发率 P 0 0234 NaitoS etal TheJournalofUrology2008 179 485 490 研究结果 不良反应 研究结论 浅表性膀胱癌TUR术后膀胱内灌注法玛新联合口服干酪乳杆菌是预防复发的一种新的治疗方法 NaitoS etal TheJournalofUrology2008 179 485 490 GurtowskaN KloskowskiT DrewaT MedSciMonit 2010 16 10 218 223 Ciprofloxacincriteriainantimicrobialprophylaxisandbladdercancerrecurrence Amongfluoroquinolones ciprofloxacinisdistinguishedbystronginhibitionoftopoisomeraseII Antiproliferativepotentialoftheciprofloxacinagainsthumanbladdercellsvariesaccordingtodrugconcentrationandtimeofincubation LowurinepHcanenhancetheantitumoreffectofciprofloxacin Ciprofloxacinenhancestheeffectofactionofdoxorubicinandepirubicin whichareusedtopreventbladdercancerrecurrenceaftertransurethralresectionofsuperficialbladdercancer Wethinkthatciprofloxacinmightbeusedforantibacterialprophylaxisandasananticanceragentinpatientswithsuperficialbladdercancer 表柔比星膀胱内灌注方案的优化 剂量优化灌注频率和疗程的优化联合用药剂型优化 Fig Thecytotoxicityofepirubicinnanoparticlesagainsthumanbladdercancercells Li ChingChang Shu ChinWu Jen WeiTsai etal InternationalJournalofPharmaceutics 2009 376 195 203 Permeabilityofepirubicinnanoparticles 小结 表柔比星高剂量膀胱内灌注的疗效优于低剂量 80mg 50mg 20mg 对于中危复发的NMIBC患者 高剂量 80mg 表柔比星长程灌注对TURBT术后肿瘤复发的预防疗效与BCG相同 对中高危复发的NMIBC患者 如果TURBT术后6小时内给予50mg 100