课件：表柔比星膀胱内灌注化疗方案的优化.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,There is no single drug that is superior with regards to efficacy. Mitomycin C, epirubicin and doxorubicin have all shown a beneficial effect (evidence: 1b).,2010 EAU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-Dein B, et al. The Journal of Urology 1997; 158:68-74.,基线特征,Ali-El-Dein B, et al. The Journal of Urology 1997; 158:68-74.,研究结果：复发率,Ali-El-Dein B, et al. The Journal of Urology 1997; 158:68-74.,研究结果：不良反应,Ali-El-Dein B, et al. The Journal of Urology 1997; 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,Saika T, et al. World J Urol 2010.,基线特征,Saika T, et al. World J Urol 2010.,研究结果：无复发生存,Saika T, et al. World J Urol 2010.,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,Saika T, et al. World J Urol 2010.,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,Moutzouris G, et al. Eur Urol Suppl 2007; 6(2): 171, Abstract 595.,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,Moutzouris G, et al. Eur Urol Suppl 2007; 6(2): 171, Abstract 595.,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,Hendricksen K, Witjes WP, Idema JG ,et al. Eur Urol，2008，53(5)：984-991.,Patients with intermediate- and high-risk urothelial cell carcinoma of the bladder, except carcinoma in situ, were randomised for adjuvant intravesical instillations with 50 mg epirubicin/50 ml NaCl for 1 h. Group 1 received 4 weekly and 5 monthly instillations (standard schedule). group 2 received the same schedule as group 1, but with an additional instillation 48 h after TURBT. group 3 received the same scheme as group 1, but with additional instillations at 9 and 12 mo (maintenance schedule).,Trkeri L, Tandr Y, al , et al. Urol Int,2010,85(3):261-5.,Comparison of the efficacy of single or double intravesical epirubicin instillation in the early postoperative period to prevent recurrences in non-muscle-invasive urothelial carcinoma of the bladder: prospective, randomized multicenter study.,primary and solitary or multiple (3 or less) Ta (grade 2-3) or T1 (grade 1-2) tumors were enrolled. A total of 299 patients from 24 institutions were randomized to receive either a single dose of 100 mg epirubicin instillation within 6 h or a second 100 mg epirubicin instillation during the 12th-18th hours after a complete TUR-BT. RESULTS: The follow-up and disease-free survival periods were 16.9 months and 16 months, respectively. CONCLUSIONS: A second intravesical epirubicin instillation did not provide any significant benefit.,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,Koga 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：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。,Koga H, et al. J Urol 2004; 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,Raitanen MP, Lukkarinen O, Finnish Multicentre Study Group. Br J Urol, 1995, 76(6): 697-701.,A controlled study of intravesical epirubicin with or without alpha 2b-interferon as prophylaxis for recurrent superficial transitional cell carcinoma of the bladder. Finnish Multicentre Study Group.,PATIENTS AND METHODS: 81 patients with superficial (stage Ta and T1), well or moderately differentiated (grades 1 and 2) TCC were randomized into three groups: Group 1 ：TUR alone; Group 2 ：50 mg epirubicin; Group 3 ：50 mg epirubicin combined with 10 MU alpha 2b-IFN, intravesically. The instillations were started 1 week after TUR and were performed weekly during the first month and then once a month for one year. RESULTS: The patients were followed for a mean of 20 months. Patients receiving intravesical chemoimmunotherapy (Group 3) had the most favourable outcome; they had comparatively lower recurrence and tumour rates, fewer patients with recurrences and, most importantly, the longest disease-free interval. Side-effects were mostly mild and transient, and no differences were found among the groups.,Malmstrom P, Wiklund F, Duchek M. et al. Journal of Urology,2008,179(4-sup1):587,ADJUVANT INTRAVESICAL EPIRUBICIN AND INTERFERON 2b IS COMPARABLE TO BCG FOR TREATMENT OF T1 TUMOURS OF THE URINARY BLADDER,The first TUR of the T1 tumour was followed within 4-6 weeks by a second-look resection including bladder mapping and resection biopsy of the prostatic urethra. Two weeks later patients received according to randomisation schedule either BCG (Oncotice) or the combination of epirubicin (Farmorubicin 50mg） and Interferon2b (100,000IU) Both regimens given as induction treatment for 6 weeks followed by maintenance therapy for 2 years. The mean duration of follow-up is presently 3.2 (0.1-7.9) years.,Naito S, et al. The Journal of Urology，2008，179:485-490.,LC：干酪乳酸菌,基线特征,Naito S, et al. The Journal of Urology 2008; 179:485-490.,研究结果：复发率,P=0.0234,Naito S, et al. The Journal of Urology 2008; 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。,Naito S, et al. The Journal of Urology 2008; 179:485-490.,Gurtowska N, Kloskowski T, Drewa T. Med Sci Monit,2010,16(10):218-223.,Ciprofloxacin criteria in antimicrobial prophylaxis and bladder cancer recurrence,Among fluoroquinolones, ciprofloxacin is distinguished by strong inhibition of topoisomerase II. Antiproliferative potential of the ciprofloxacin against human bladder cells varies according to drug concentration and time of incubation. Low urine pH can enhance the antitumor effect of ciprofloxacin. Ciprofloxacin enhances the effect of action of doxorubicin and epirubicin, which are used to prevent bladder cancer recurrence after transurethral resection of superficial bladder cancer. We think that ciprofloxacin might be used for antibacterial prophylaxis and as an anticancer agent in patients with superficial bladder cancer.,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. The cytotoxicity of epirubicin nanoparticles against human bladder cancer cells.,Li-Ching Chang, Shu-ChinWu, Jen-Wei Tsai, et al. International Journal of Pharmaceutics，2009，376 ：195203,Permeability of epirubicin nanoparticles,小 结,表柔比星高剂量膀胱