表柔比星膀胱内灌注化疗方案的优化ppt课件.ppt

表柔比星膀胱内灌注方案的优化表柔比星膀胱内灌注方案的优化福建省立医院泌尿外科福建省立医院泌尿外科李李 涛涛There is no single drug that is superior with regards to There is no single drug that is superior with regards to efficacy.Mitomycin C,epirubicin and doxorubicin have all efficacy.Mitomycin C,epirubicin and doxorubicin have all shown a beneficial effect(evidence:1b).shown a beneficial effect(evidence:1b).2010 EAU2010 EAU对对NMIBCNMIBC的治疗的推荐的治疗的推荐TURBT+TURBT+即刻单次膀胱内灌注即刻单次膀胱内灌注复发复发复发复发/进展进展根治性膀胱切除术根治性膀胱切除术化疗化疗BCG+BCG+维持治疗维持治疗单瘤、原发单瘤、原发低分级低分级 TaTa多发、复发多发、复发低分级肿瘤低分级肿瘤任何任何T1T1和和/或或G3G3和和/或原位癌或原位癌观察观察复发复发/进展进展BCG+BCG+维持治疗维持治疗低危低危中危中危高危高危TURBT+TURBT+单次化疗单次化疗TURBT+TURBT+单次化疗单次化疗表柔比星膀胱内灌注方案的优化表柔比星膀胱内灌注方案的优化提高疗效（尤其是能否替代提高疗效（尤其是能否替代BCGBCG？）？）减少不良反应减少不良反应增加便利性（减少不必要的灌注次数）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表柔比星膀胱内灌注方案的优化剂量优化剂量优化灌注频率和疗程的优化灌注频率和疗程的优化联合用药联合用药剂型优化剂型优化比较法玛新不同剂量膀胱内灌注给药的研究比较法玛新不同剂量膀胱内灌注给药的研究50mg/50ml,80mg/50ml50mg/50ml,80mg/50mlAli-El-Dein B,et al.The Journal of Urology 1997;158:68-74.Ali-El-Dein B,et al.The Journal of Urology 1997;158:68-74.膀胱内灌注在术后膀胱内灌注在术后7-147-14天开始，每周天开始，每周进行一次，进行进行一次，进行8 8周周然后每月进行一次至一年疗程结束然后每月进行一次至一年疗程结束随访时间为随访时间为1212月月-48-48月月(平均为平均为30.130.1月月)组组1 1：法玛新法玛新50mg/50ml50mg/50ml生理盐水生理盐水组组2 2：法玛新法玛新80mg/50ml80mg/50ml生理盐水生理盐水组组3 3：阿霉素阿霉素50mg/50ml50mg/50ml生理盐水生理盐水组组4 4：未接受未接受任何辅助治疗任何辅助治疗浅表性膀胱癌患者浅表性膀胱癌患者R R手术手术基线特征基线特征组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0.05p0.05研究结果：不良反应研究结果：不良反应Ali-El-Dein B,et al.The Journal of Urology 1997;158:68-74.Ali-El-Dein B,et al.The Journal of Urology 1997;158:68-74.法玛新法玛新50mg50mg组组 (n=64)(n=64)不良反应发生例数不良反应发生例数 (个个)研究结论：研究结论：法玛新的剂量和疗效正相关法玛新的剂量和疗效正相关临床推荐临床推荐TURBTTURBT术后可常规使用术后可常规使用50mg50mg法玛新法玛新 ，最高可以用到，最高可以用到80mg80mg法玛新局部刺激性小，严重不良反法玛新局部刺激性小，严重不良反应少应少比较比较Ta/T1Ta/T1期移行细胞膀胱癌患者期移行细胞膀胱癌患者接受接受TURBTTURBT术后两次法玛新膀胱内灌注研究术后两次法玛新膀胱内灌注研究Saika T,et al.World J Urol 2010.Saika T,et al.World J Urol 2010.主要终点：至首次复主要终点：至首次复发时间发时间N=303N=303A.TURBT+A.TURBT+法玛新法玛新 20 mg/40 ml(N=79)20 mg/40 ml(N=79)TURBTTURBT术后术后1 1小时内即刻小时内即刻灌注灌注1 1次，第二天早晨灌次，第二天早晨灌注注1 1次，术后次，术后2424小时内灌小时内灌注注2 2次次C.C.仅仅TURBTTURBT(N=(N=7777)Ta/T1Ta/T1 移行细胞癌移行细胞癌NMIBC NMIBC 患者患者B.TURBT+B.TURBT+法玛新法玛新 50 mg/100 ml50 mg/100 ml (N=84)(N=84)TURBTTURBT术后术后1 1小时内即刻小时内即刻灌注灌注1 1次，第二天早晨灌次，第二天早晨灌注注1 1次，术后次，术后2424小时内灌小时内灌注注2 2次次R R中位随访中位随访4444个月个月基线特征基线特征ABC总计中位年龄(岁)69697169性别(男性/女性)67/1680/1074/10221/36原发/复发50/3351/3950/34151/106单瘤/多瘤38/4538/5236/48112/145原发单瘤/原发多瘤28/2228/2324/2680/71复发单瘤/复发多瘤10/2310/2912/2232/74最大肿瘤直径1cm49%56%48%51%肿瘤分级(G1/G2/G3)21/49/1230/42/1826/44/1477/135/44肿瘤分期(Ta/T1)45/3654/3654/30153/102总计839084257Saika T,et al.World J Urol 2010.Saika T,et al.World J Urol 2010.研究结果：无复发生存研究结果：无复发生存Saika T,et al.World J Urol 2010.Saika T,et al.World J Urol 2010.ABC中位RFS(月)243813时间时间 (年年)generalized generalized Wilcoxon Wilcoxon testesB vs.C,B vs.C,P=0.04P=0.0410010080806060404020200 00.00.01.01.02.02.03.03.04.04.05.05.0A A 法玛新法玛新 20mg20mg无复发率无复发率 (%)(%)B B 法玛新法玛新 50mg50mgC C 无法玛新无法玛新研究结果：不良事件研究结果：不良事件研究结论：研究结论：TURBTTURBT后后2424小时内给予膀胱内灌注两次法玛新小时内给予膀胱内灌注两次法玛新50mg50mg比比两次灌注两次灌注20mg20mg可进一步延长复发时间，且副作用很小。可进一步延长复发时间，且副作用很小。法玛新20法玛新50P1级膀胱刺激性(%)22.935.60.1061级外周红细胞减少(n)22-1级血清转氨酶升高(n)13-1级外周白细胞减少1-所有不良反应均所有不良反应均可逆可逆Saika T,et al.World J Urol 2010.Saika T,et al.World J Urol 2010.比较高剂量法玛新膀胱内灌注与比较高剂量法玛新膀胱内灌注与BCGBCG对中危浅表性膀胱癌患者预防作用的研究对中危浅表性膀胱癌患者预防作用的研究Moutzouris G,et al.Eur Urol Suppl 2007;6(2):171,Abstract 595.Moutzouris G,et al.Eur Urol Suppl 2007;6(2):171,Abstract 595.DFSDFS复发复发安全性安全性N=234N=234法玛新法玛新80mg/50ml 80mg/50ml 生理盐水生理盐水 (N=121)(N=121)BCGBCG(N=113)(N=113)TURBTTURBT术后术后原发或复发原发或复发Ta G2-3,T1 Ta G2-3,T1 G1-2 G1-2 TCCTCC患者患者R R每周膀胱内灌注，共六周；后续第每周膀胱内灌注，共六周；后续第3/6/12/18/24/30/363/6/12/18/24/30/36个月给予个月给予3 3次每周膀胱内灌注次每周膀胱内灌注中位随访中位随访2121个月个月前瞻性随机对照研究前瞻性随机对照研究研究结果研究结果研究结论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对于中危NMIBCNMIBC患者患者TURBTTURBT术后复发的预防疗效与术后复发的预防疗效与BCGBCG相同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-Moutzouris G,et al.Eur Urol Suppl Moutzouris G,et al.Eur Urol Suppl 2007;6(2):171,Abstract 595.2007;6(2):171,Abstract 595.表柔比星膀胱内灌注方案的优化表柔比星膀胱内灌注方案的优化剂量优化剂量优化灌注频率和疗程的优化灌注频率和疗程的优化联合用药联合用药剂型优化剂型优化Hendricksen K,Witjes WP,Idema JG,et al.Hendricksen K,Witjes WP,Idema JG,et al.Eur UrolEur Urol，20082008，53(5)53(5)：984-991.984-991.Patients with intermediate-and high-risk urothelial cell Patients with intermediate-and high-risk urothelial cell carcinoma of the bladder,except carcinoma in situ,were carcinoma of the bladder,except carcinoma in situ,were randomised for adjuvant intravesical instillations with randomised for adjuvant intravesical instillations with 50 mg epirubicin/50 ml NaCl for 1 h.50 mg epirubicin/50 ml NaCl for 1 h.Group 1 received 4 weekly and 5 monthly instillations Group 1 received 4 weekly and 5 monthly instillations(standard schedule).(standard schedule).group 2 received the same schedule as group 1,but with group 2 received the same schedule as group 1,but with an additional instillation 48 h after TURBT.an additional instillation 48 h after TURBT.group 3 received the same scheme as group 1,but with group 3 received the same scheme as group 1,but with additional instillations at 9 and 12 mo(maintenance additional instillations at 9 and 12 mo(maintenance schedule).schedule).group 1group 2group 3 5-yr recurrence free44.4%42.7%45.0%5-yr progression free90.0%87.7%88.2%T T rkeri L,Tanrkeri L,Tand dr Y,r Y,al al ,et,et al.al.Urol Int,2010,85(3):261-5.Urol Int,2010,85(3):261-5.Comparison of the efficacy of single or double Comparison of the efficacy of single or double intravesical epirubicin instillation in the early intravesical epirubicin instillation in the early postoperative period to prevent recurrences in non-muscle-postoperative period to prevent recurrences in non-muscle-invasive urothelial carcinoma of the bladder:prospective,invasive urothelial carcinoma of the bladder:prospective,randomized multicenter study.randomized multicenter study.primary and solitary or multiple(3 or less)Ta(grade 2-3)primary and solitary or multiple(3 or less)Ta(grade 2-3)or T1(grade 1-2)tumors were enrolled.or T1(grade 1-2)tumors were enrolled.A total of 299 patients from 24 institutions were randomized A total of 299 patients from 24 institutions were randomized to receive either a single dose of 100 mg epirubicin to receive either a single dose of 100 mg epirubicin instillation within 6 h or a second 100 mg epirubicin instillation within 6 h or a second 100 mg epirubicin instillation during the 12th-18th hours after a complete TUR-instillation during the 12th-18th hours after a complete TUR-BT.BT.RESULTS:The follow-up and disease-free survival periods were RESULTS:The follow-up and disease-free survival periods were 16.9 months and 16 months,respectively.16.9 months and 16 months,respectively.CONCLUSIONS:A second intravesical epirubicin instillation CONCLUSIONS:A second intravesical epirubicin instillation did not provide any significant benefit.did not provide any significant benefit.比较比较Ta/T1Ta/T1膀胱癌膀胱癌TURTUR术后术后长疗程与短疗程法玛新膀胱内灌注的研究长疗程与短疗程法玛新膀胱内灌注的研究Koga H,et al.J Urol 2004;171(1):153-157.Koga H,et al.J Urol 2004;171(1):153-157.N=150N=150复发率复发率安全性安全性1 1年：法玛新年：法玛新30mg/30ml 30mg/30ml 生理盐水生理盐水19(N=77)19(N=77)3 3个月：法玛新个月：法玛新30mg/30ml 30mg/30ml 生理盐水生理盐水9(N=73)9(N=73)TURTUR术后术后Ta/T1Ta/T1膀胱癌患膀胱癌患者者R R膀胱内灌注次数1年组3个月组1TUR后5510：每2周59：每2周1119：每月1年组3个月组5年RFS()85.263.9Koga H,et al.J Urol 2004;171(1):153-157.Koga H,et al.J Urol 2004;171(1):153-157.研究结果：复发率研究结果：复发率术后时间术后时间 (月月)P=0.00P=0.005 5无肿瘤复发患者比例无肿瘤复发患者比例 (%)(%)10010080806060404020200 00 01212242436364848606072721 1年组年组3 3个月组个月组研究结果：不良反应研究结果：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（研究结论：与短疗程法玛新膀胱内灌注相比，长疗程（1 1年）年）法玛新明显降低复发率，且不增加严重不良反应。法玛新明显降低复发率，且不增加严重不良反应。Koga H,et al.J Urol 2004;171(1):153-157.Koga H,et al.J Urol 2004;171(1):153-157.严重局部不良反应发生率严重局部不良反应发生率P=NSP=NS表柔比星膀胱内灌注方案的优化表柔比星膀胱内灌注方案的优化剂量优化剂量优化灌注频率和疗程的优化灌注频率和疗程的优化联合用药联合用药剂型优化剂型优化Raitanen MP,Lukkarinen O,Finnish Multicentre Raitanen MP,Lukkarinen O,Finnish Multicentre Study Group.Study Group.Br J Urol,1995,76(6):697-701.Br J Urol,1995,76(6):697-701.A controlled study of intravesical epirubicin with A controlled study of intravesical epirubicin with or without alpha 2b-interferon as prophylaxis for or without alpha 2b-interferon as prophylaxis for recurrent superficial transitional cell carcinoma of recurrent superficial transitional cell carcinoma of the bladder.Finnish Multicentre Study Group.the bladder.Finnish Multicentre Study Group.PATIENTS AND METHODS:PATIENTS AND METHODS:81 patients with superficial(stage Ta and T1),well or 81 patients with superficial(stage Ta and T1),well or moderately differentiated(grades 1 and 2)TCC were moderately differentiated(grades 1 and 2)TCC were randomized into three groups:randomized into three groups:Group 1 Group 1：TUR alone;TUR alone;Group 2 Group 2：50 mg epirubicin;50 mg epirubicin;Group 3 Group 3：50 mg epirubicin combined with 10 MU alpha 2b-50 mg epirubicin combined with 10 MU alpha 2b-IFN,intravesically.IFN,intravesically.The instillations were started 1 week after TUR and were The instillations were started 1 week after TUR and were performed weekly during the first month and then once a performed weekly during the first month and then once a month for one year.month for one year.RESULTS:RESULTS:The patients were followed for a mean of 20 months.The patients were followed for a mean of 20 months.Patients receiving intravesical chemoimmunotherapy(Group Patients receiving intravesical chemoimmunotherapy(Group 3)had the most favourable outcome;they had comparatively 3)had the most favourable outcome;they had comparatively lower recurrence and tumour rates,fewer patients with lower recurrence and tumour rates,fewer patients with recurrences and,most importantly,the longest disease-free recurrences and,most importantly,the longest disease-free interval.Side-effects were mostly mild and transient,and interval.Side-effects were mostly mild and transient,and no differences were found among the groups.no differences were found among the groups.Malmstrom P,Wiklund F,Duchek M.et al.Malmstrom P,Wiklund F,Duchek M.et al.Journal of Urology,2008,179(4-sup1):587 Journal of Urology,2008,179(4-sup1):587 ADJUVANT INTRAVESICAL EPIRUBICIN AND INTERFERON 2b ADJUVANT INTRAVESICAL EPIRUBICIN AND INTERFERON 2b IS COMPARABLE TO BCG FOR TREATMENT OF T1 TUMOURS OF THE IS COMPARABLE TO BCG FOR TREATMENT OF T1 TUMOURS OF THE URINARY BLADDER URINARY BLADDER BCGEpirubicin+Interferon2bN(T1 bladder cancer)117118Recurrence25%23%progression11%9%Worsened urinary symptoms at 6 months follow-up24%16%The first TUR of the T1 tumour was followed within 4-6 The first TUR of the T1 tumour was followed within 4-6 weeks by a second-look resection including bladder mapping weeks by a second-look resection including bladder mapping and resection biopsy of the prostatic urethra.Two weeks and resection biopsy of the prostatic urethra.Two weeks later patients received according to randomisation schedule later patients received according to randomisation schedule either BCG(Oncotice)or the combination of epirubicin either BCG(Oncotice)or the combination of epirubicin(Farmorubicin 50mg(Farmorubicin 50mg）and Interferon2b(100,000IU)Both and Interferon2b(100,000IU)Both regimens given as induction treatment for 6 weeks followed regimens given as induction treatment for 6 weeks followed by maintenance therapy for 2 years.The mean duration of by maintenance therapy for 2 years.The mean duration of follow-up is presently 3.2(0.1-7.9)years.follow-up is presently 3.2(0.1-7.9)years.Naito S,et al.The Journal of UrologyNaito S,et al.The Journal of Urology，20082008，179:485-490.179:485-490.LCLC：干酪：干酪乳酸菌乳酸菌多中心、前瞻性、随机对照研究多中心、前瞻性、随机对照研究临床诊断为浅表性膀胱癌患者临床诊断为浅表性膀胱癌患者TURTUR术后术后1 1周内周内膀胱内灌注膀胱内灌注(法玛新法玛新30mg/30ml30mg/30ml生理盐水生理盐水)共共2 2次次R R法玛新组法玛新组 (N=102)(N=102)术后术后3 3月内附加月内附加6 6次法玛新膀胱内灌次法玛新膀胱内灌注注法玛新联合法玛新联合LCLC组组 (N=100)(N=100)术后术后3 3月内附加月内附加6 6次法次法玛新膀胱内灌注玛新膀胱内灌注口服干酪乳杆菌口服干酪乳杆菌3mg/3mg/天天 持续持续1 1年年评估复发、疾病进展、预后及药物不良评估复发、疾病进展、预后及药物不良反应反应基线特征基线特征Naito S,et al.The Journal of Urology 2008;179:485-490.Naito S,et al.The Journal of Urology 2008;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 80mg 50mg20mg50mg20mg）。）。p对于中危复发的对于中危复发的NMIBCNMIBC患者，高剂量（患者，高剂量（80mg80mg）表柔比星长程灌）表柔比星长程灌注对注对TURBTTURBT术后肿瘤复发的预防疗效与术后肿瘤复发的预防疗效与BCGBCG相同。相同。p对中高危复发的对中高危复发的NMIBCNMIBC患者，如果患者，如果TURBTTURBT术后术后6 6小时内给予小时内给予50mg-50mg-100mg100mg表柔比星膀胱内灌注，则在表柔比星膀胱内灌注，则在2424或或4848小时内给予第二次膀小时内给予第二次膀胱内灌注，并不能进一步降低肿瘤的复发率。胱内灌注，并不能进一步降低肿瘤的复发率。p对中高危复发的对中高危复发的NMIBCNMIBC患者，表柔比星长疗程（至少半年）灌患者，表柔比星长疗程（至少半年）灌注的疗效优于短疗程；而采用低剂量（注的疗效优于短疗程；而采用低剂量（30mg30mg）灌注，则最好灌）灌注，则最好灌注疗程至少注疗程至少1 1年。年。小小 结结p联合联合IFN-2bIFN-2b膀胱内灌注可提高表柔比星的疗效；对膀胱内灌注可提高表柔比星的疗效；对T1T1肿瘤，肿瘤，该联合方案的长程（该联合方案的长程（2 2年）灌注对年）灌注对TURBTTURBT术后肿瘤复发的预防疗术后肿瘤复发的预防疗效与效与BCGBCG相同。相同。p联合口服免疫调节剂干酪乳杆菌能进一步提高表柔比星膀胱内联合口服免疫调节剂干酪乳杆菌能进一步提高表柔比星膀胱内灌注的疗效。灌注的疗效。p尚未明确：环丙沙星能提高表柔比星的疗效？表柔比星纳米颗尚未明确：环丙沙星能提高表柔比星的疗效？表柔比星纳米颗粒剂型膀胱内灌注的疗效优于表柔比星水溶剂？粒剂型膀胱内灌注的疗效优于表柔比星水溶剂？谢谢！谢谢！谢谢！谢谢！后面内容直接删除就行后面内容直接删除就行资料可以编辑修改使用资料可以编辑修改使用资料可以编辑修改使用资料可以编辑修改使用主要经营：网络软件设计、图文设计制作、主要经营：网络软件设计、图文设计制作、发布广告等发布广告等公司秉着以优质的服务对待每一位客户，做公司秉着以优质的服务对待每一位客户，做到让客户满意！到让客户满意！致力于数据挖掘，合同简历、论文写作、致力于数据挖掘，合同简历、论文写作、PPTPPT设计、计划书、策划案、学习课件、各设计、计划书、策划案、学习课件、各类模板等方方面面，打造全网一站式需求类模板等方方面面，打造全网一站式需求The user can demonstrate on a projector The user can demonstrate on a projector or computer,or print the presentation or computer,or print the 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