目的:回顾目前的文献,以支持在环磷酰胺治疗的全身性自身免疫性疾病和全身性血管炎患者中使用mesna作为出血性膀胱炎和膀胱癌的预防性治疗。
方法:文章的搜索是通过MEDLINE系统进行的,LILACS,科克伦图书馆,和Embase数据库。只选择了英文文章。对于可用的记录,标题和摘要由两名研究者独立选择.
结果:选择18项研究进行分析。环磷酰胺的已知不良反应是血液学毒性,感染,性腺毒性,致畸性,恶性肿瘤和出血性膀胱炎的风险增加。长期毒性高度依赖于环磷酰胺累积剂量。长期暴露和累积剂量超过36g时,膀胱癌的风险尤其高。停药后数年风险仍然很高。出血性膀胱炎与累积剂量高度相关,其发病率范围在12%至41%之间。但在环磷酰胺剂量减少的新方案中,其似乎更低.没有发现随机对照试验分析mesna在系统性自身免疫性风湿性疾病和系统性血管炎中的使用。回顾性研究产生了相互矛盾的结果。结果为阳性的非对照前瞻性研究被认为存在高偏倚风险。没有证据支持在环磷酰胺治疗自身免疫性疾病或系统性血管炎期间使用mesna预防出血性膀胱炎和膀胱癌。在高累积环磷酰胺剂量的情况下(即,>30g),液体摄入受限的患者,神经源性膀胱,口服抗凝剂治疗,和慢性肾病,可以考虑mesna。
结论:目前的证据不足以支持在接受环磷酰胺治疗的系统性自身免疫性疾病和系统性血管炎患者中常规使用mesna预防出血性膀胱炎和膀胱癌。可以针对选定的情况考虑使用。
To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide.
The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators.
Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered.
The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.