Uozumi J, Koikawa Y, Yasumasu T, Tokuda N, Kumazawa J
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Int J Urol. 1996 Sep;3(5):343-7. doi: 10.1111/j.1442-2042.1996.tb00551.x.
Many attempts have been made to reduce the nephrotoxicity of the anticancer agent cisplatin but the number of clinically useful modalities is very limited. Our previous experiments demonstrated that in rats methylprednisolone significantly reduces the nephrotoxicity caused by cisplatin. The present clinical study was conducted to confirm the protective effects of methylprednisolone against cisplatin nephrotoxicity.
Fourteen patients with urothelial tumors were injected with cisplatin according to the methotrexate, vinblastine, adriamycin, cisplatin (MVAC) therapy. Methylprednisolone was not administered during the first course of chemotherapy to provide a control, but was given in a dose of 2000 mg 2-3 hours before cisplatin during the second course of chemotherapy (treatment period) in each patient. Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltranspeptidase (GGTP), serum creatinine, and creatinine clearance (Ccr) were determined as indicators of the nephrotoxicity of cisplatin. Results were statistically analyzed by a paired t test to compare the nephrotoxic effects of cisplatin during the first course of chemotherapy (control period) with those during the second course of chemotherapy (treatment period).
Methylprednisolone did not significantly inhibit the elevation in urinary enzyme excretion or serum creatinine levels following the cisplatin injection. However, the Ccr level after cisplatin infusion in the treatment period was significantly higher than that observed in the control period.
The protective effects of methylprednisolone against cisplatin nephrotoxicity were indicated in this prospective clinical study.
人们已经进行了许多尝试来降低抗癌药物顺铂的肾毒性，但临床上有用的方法数量非常有限。我们之前的实验表明，在大鼠中甲基泼尼松龙可显著降低顺铂引起的肾毒性。本临床研究旨在证实甲基泼尼松龙对顺铂肾毒性的保护作用。
14例尿路上皮肿瘤患者按照甲氨蝶呤、长春碱、阿霉素、顺铂（MVAC）疗法注射顺铂。在第一个化疗疗程中不给予甲基泼尼松龙作为对照，而在每个患者的第二个化疗疗程（治疗期）中，在顺铂注射前2 - 3小时给予2000 mg的剂量。测定尿N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）和γ - 谷氨酰转肽酶（GGTP）的排泄量、血清肌酐以及肌酐清除率（Ccr），作为顺铂肾毒性的指标。通过配对t检验对结果进行统计学分析，以比较第一个化疗疗程（对照期）和顺铂第二个化疗疗程（治疗期）的肾毒性作用。
甲基泼尼松龙并未显著抑制顺铂注射后尿酶排泄或血清肌酐水平的升高。然而，治疗期顺铂输注后的Ccr水平显著高于对照期。
这项前瞻性临床研究表明了甲基泼尼松龙对顺铂肾毒性的保护作用。
