The protective effect of methylprednisolone against cisplatin-induced nephrotoxicity in patients with urothelial tumors.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
The protective effects of methylprednisolone against cisplatin nephrotoxicity were indicated in this prospective clinical study.
Uozumi
J
J
Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Koikawa
Y
Y
Yasumasu
T
T
Tokuda
N
N
Kumazawa
J
J
D000118:Acetylglucosaminidase / Q000652:urine; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000009:adverse effects; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects; D008775:Methylprednisolone / Q000627:therapeutic use*; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D014747:Vinblastine / Q000009:adverse effects; D005723:gamma-Glutamyltransferase / Q000652:urine
D005938:Glucocorticoids; D014747:Vinblastine; D004317:Doxorubicin; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D002945:Cisplatin; D008775:Methylprednisolone; D008727:Methotrexate