吉西他滨较丝裂霉素治疗TURBT后非肌层浸润性膀胱癌的复发率低、毒副作用小:基于随机对照试验的荟萃分析

Gemcitabine Has a Lower Recurrence Rate and Less Side Effects than Mitomycin for Non-muscular Invasive Bladder Cancer after TURBT:a Meta-analysis of Randomized Controlled Trials

背景吉西他滨(GEM)和丝裂霉素(MMC)均为经尿道膀胱肿瘤电切术(TURBT)后治疗非肌层浸润性膀胱癌(NMIBC)的化疗药物,目前对于两种药物的临床疗效和毒副作用差异尚无定论。目的评估两种药物治疗TURBT后NMIBC的有效性与安全性。方法计算机系统检索Pub Med,EMBase,Web of Science,The Cochrane Library,中国知网(CNKI),万方数据知识服务平台,中国生物医学文献数据库,维普网(检索时限为建库至2020-10-01)中关于GEM和MMC治疗TURBT后的NMIBC的随机对照试验(RCT),提取第一作者、发表年份、研究设计类型、证据等级、年龄、样本量、肿瘤生长情况、肿瘤WHO分级、TNM分期、药物灌注剂量、肿瘤复发情况(术后1年肿瘤复发率或术后2年肿瘤复发率)、灌注后的不良事件(AE)[膀胱刺激征、血尿、肝肾功能损害,其他并发症(皮疹、恶心呕吐、耻骨上疼痛等)]等资料,检索年限为数据库建立到2020-10-01。根据TURBT后用药情况分为GEM组、MMC组,并对两组患者的术后1年、2年肿瘤复发率及灌注化疗后AE发生率进行Meta分析。结果累计纳入7篇RCT,共484例患者,经Jadad量表评估均为高质量研究。Meta分析结果显示,两组患者术后1年肿瘤复发率比较,差异无统计学意义[OR=0.86,95%CI(0.29,2.56),P=0.17];GEM组术后2年肿瘤复发率[OR=0.37,95%CI(0.23,0.59),P=0.01]、灌注化疗后总AE发生率[OR=0.28,95%CI(0.18,0.43),P=0.01]、膀胱刺激征发生率[OR=0.30,95%CI(0.17,0.54),P=0.04]、其他并发症(皮疹、恶心呕吐、耻骨上疼痛等)发生率[OR=0.46,95%CI(0.24,0.88),P=0.01]低于MMC组,两组患者术后血尿发生率[OR=0.52,95%CI(0.21,1.26),P=0.22]和肝肾功能损害发生率[OR=0.51,95%CI(0.29,0.85),P=0.16]比较,差异无统计学意义。结论 GEM拥有更低的术后肿瘤复发率和毒副作用发生率,是安全且有效的抗肿瘤化疗药物。

Background Gemcitabine and mitomycin are both chemotherapy drugs for non-muscular invasive bladder cancer(NMIBC)after transurethral resection of bladder tumor(TURBT). However,no final conclusion has been reached on these two drugs in terms of differences in clinical efficacy and safety. Objective To evaluate the effectiveness and safety of gemcitabine versus mitomycin in the treatment of NMIBC after TURBT. Methods Published randomized controlled studies(RCT)comparing gemcitabine and mitomycin for NMIBC after TURBT were searched in databases of PubMed,EMBase,Web of Science,The Cochrane Library,CNKI,Wanfang Data,SinoMed,and CQVIP from inception to 2020-10-01,and enrolled according to the inclusion and exclusion criteria.Data of included RCT were extracted,including the first author,publication year,design,level of evidence,sample age,sample size,tumor growth,WHO classification,TNM staging,drug infusion dosage,cancer recurrence(recurrence within one and two years after surgery),and chemotherapy perfusion-related adverse events(bladder irritation,hematuria,liver and kidney damage,rash,nausea and vomiting,suprapubic pain). The patients were divided into GEM group and MMC group according to the drug use after TURBT. Meta-analysis of recurrence within one and two years after surgery and incidence of chemotherapy perfusion-related adverse events was performed in two groups. Results A total of seven RCT were included,involving 484 patients,with high quality rated by the Jadad Scale. Meta-analysis showed no statistically significant difference in one-year recurrence rate between the two groups of patients[OR=0.86,95%CI(0.29,2.56),P=0.17]. But gemcitabine group gained more benefits in reducing the two-year recurrence rate[OR=0.37,95%CI(0.23,0.59),P=0.01]. Furthermore,gemcitabine group demonstrated lower overall incidence of chemotherapy perfusion-related adverse events[OR=0.28,95%CI(0.18,0.43),P=0.01],lower incidence of bladder irritation[OR=0.30,95%CI(0.17,0.54),P=0.04]as well as lower incidence of other complications(rash,nausea and vomiting,suprapubic pain)[OR=0.46,95%CI(0.24,0.88),P=0.01]. There were no statistically significant intergroup differences in the incidence of postoperative hematuria[OR=0.52,95%CI(0.21,1.26),P=0.22]and liver and kidney damage[OR=0.51,95%CI(0.29,0.85),P=0.16]. Conclusion Gemcitabine may be more effective and safe for NMIBC after TURBT,owing to its better effects on lowering the recurrence rate and incidence of adverse events.