Shibuya M, Hirosawa A, Niitani H
Dept. of Respiratory Disease, Nippon Medical School.
Gan To Kagaku Ryoho. 1990 Apr;17(4 Pt 2):950-6.
Renal dysfunction and urinary disorders are the most troublesome adverse reaction to anticancer agents such as cisplatin (CDDP) and ifosfamide (IFM). A number of antidotes such as sodium thiosulfate (STS), WR-2721, thiourea, diethyldithiocarbamate and bismuth subnitrate have been tested to reduce the nephrotoxicity of CDDP. One notable method previously reported by Baba et al. and Pfeifle et al involves the i.v. administration of STS to prevent the nephrotoxicity of CDDP given locally. Since STS has been proven clinically effective in reducing such side effects, we initiated a study of STS in patients with advanced non-small-cell lung carcinoma who were given a combination of CDDP and vindesine (VDS) systemically. Urinary levels of beta 2-microglobulin (BMG) and N-acetyl-beta-D-glucosaminidase (NAG) were measured as an index of proximal tubular function. Analysis of both levels indicated that STS suppressed CDDP nephrotoxicity to a minimal level. Therefore, the present study clearly demonstrates that systemic administration of STS reduces the side effects of CDDP to a minimal level without impairing its antitumor activity and that STS treatment is applicable in a repeated chemotherapy using CDDP alone or in combination with other antitumor agents. Furthermore, it has been reported that urinastatin and fosfomycin may exert potent effects to reduce untoward nephrotoxicity of CDDP. IFM causes urinary disorders such as hematuria, reducing its clinical usefulness, Sodium 2-mercaptoethane sulfonate (mesna) is the thiol compound which binds specifically to the urinary toxic metabolites of IFM, and thereby decreases the undesirable effect of IFM on the lower urinary tract, especially on the bladder. Recently, it was reported by a Osaka mesna study group that mesna is useful for the prevention of IMF-induced urinary disorders. It was considered that above new treatments were required in repeating chemotherapy which induced urogenital toxicity.
肾功能不全和泌尿系统疾病是顺铂（CDDP）和异环磷酰胺（IFM）等抗癌药物最棘手的不良反应。人们已经测试了多种解毒剂，如硫代硫酸钠（STS）、WR-2721、硫脲、二乙基二硫代氨基甲酸盐和次硝酸铋，以降低CDDP的肾毒性。Baba等人和Pfeifle等人之前报道的一种值得注意的方法是静脉注射STS，以预防局部给予CDDP时的肾毒性。由于STS已被临床证明在减少此类副作用方面有效，我们启动了一项针对晚期非小细胞肺癌患者的研究，这些患者接受了CDDP和长春地辛（VDS）的联合全身给药。测量尿中β2-微球蛋白（BMG）和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）的水平，作为近端肾小管功能的指标。对这两个水平的分析表明，STS将CDDP肾毒性抑制到最低水平。因此，本研究清楚地表明，全身给药STS可将CDDP的副作用降低到最低水平，而不会损害其抗肿瘤活性，并且STS治疗适用于单独使用CDDP或与其他抗肿瘤药物联合的重复化疗。此外，据报道，乌司他丁和磷霉素可能对降低CDDP的不良肾毒性有显著作用。IFM会导致血尿等泌尿系统疾病，降低其临床实用性。2-巯基乙烷磺酸钠（美司钠）是一种硫醇化合物，它与IFM的尿毒性代谢产物特异性结合，从而降低IFM对下尿路，尤其是膀胱的不良影响。最近，大阪美司钠研究小组报道美司钠对预防IFM引起的泌尿系统疾病有用。人们认为，在重复诱导泌尿生殖系统毒性的化疗中需要上述新的治疗方法。
