Siu L L, Moore M J
Department of Medicine, Princess Margaret Hospital, Toronto, Ontario, Canada.
Support Care Cancer. 1998 Mar;6(2):144-54. doi: 10.1007/s005200050149.
The purpose of this study was to make evidence-based recommendations regarding the mode, dosage and schedule of delivery of concomitant mesna (sodium-2-mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial toxicity. A critical review of the literature from 1966 to 1996 was undertaken on mesna administration via the intravenous, oral, or combined modality routes. Outcome measures of urinary symptoms and macrohematuria were emphasized, since these endpoints of urotoxicity are most clinically relevant. The quality of evidence obtained from published clinical research was evaluated based on guidelines developed by the Canadian Task Force on the Periodic Health Examination. Recommendations are now made according to the strength of available evidence on the proper usage of mesna as a protective agent against ifosfamide-induced urotoxicity. There is good evidence that the use of mesna significantly reduces urinary symptoms of dysuria and frequency, as well as the incidences of macrohematuria and microhematuria, when administered concurrently with any dosage of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is superior to standard prophylaxis with vigorous hydration and alkalinization of urine. A commonly used schedule of intravenous mesna involves a dose equal to 60% of the total ifosfamide dose, divided into three aliquots and administered at 0 h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in some tested schedules is equivalent to intravenous mesna alone, but the optimal schedule and dosage of combined formulation have not yet been established. There is fair indirect but no direct evidence that oral mesna alone is equivalent to intravenous mesna or combined modality use. Further research issues, such as patient compliance with oral mesna and other routes of mesna delivery, are discussed. Ongoing study in the appropriate use of mesna is needed to maximize its value as a uroprotective agent in the clinical setting.
本研究的目的是就同时使用美司钠（2-巯基乙烷磺酸钠）的方式、剂量和给药方案提供循证建议，以预防异环磷酰胺引起的尿路上皮毒性。对1966年至1996年期间有关通过静脉、口服或联合方式给药美司钠的文献进行了严格综述。重点关注了泌尿系统症状和肉眼血尿等结局指标，因为这些尿毒性终点在临床上最为相关。根据加拿大定期健康检查特别工作组制定的指南，对已发表的临床研究获得的证据质量进行了评估。现在根据现有证据的强度，就美司钠作为预防异环磷酰胺引起的尿毒性的保护剂的正确使用提出建议。有充分证据表明，无论肿瘤部位如何，与任何剂量的异环磷酰胺同时给药时，使用美司钠可显著减轻尿痛和尿频等泌尿系统症状，以及肉眼血尿和镜下血尿的发生率。静脉或口服给予美司钠优于用积极补液和尿液碱化进行的标准预防。常用的静脉注射美司钠方案是给予相当于异环磷酰胺总剂量60%的剂量，分为三等份，在异环磷酰胺给药后0小时、4小时和8小时给药。在一些测试方案中给予的口服和静脉联合使用美司钠与单独静脉注射美司钠等效，但联合制剂的最佳方案和剂量尚未确定。有合理的间接但无直接证据表明单独口服美司钠与静脉注射美司钠或联合使用等效。还讨论了进一步的研究问题，如患者对口服美司钠的依从性和美司钠的其他给药途径。需要对美司钠的恰当使用进行持续研究，以在临床环境中最大限度地发挥其作为尿路保护剂的价值。
