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Preventive effect of urinastatin on cisplatin-induced nephrotoxicity
Authors:H Kobayashi  H Ishizuka  Y Hirashima  H Ohi  H Demukai  M Moniwa  M Maeda  T Kobayashi  T Terao  Y Kawashima
Institution:Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine.
Abstract:Anticancer chemotherapy with cisplatin (CDD) as the main drug (combined with adriamycin (ADM) and cyclophosphamide (CPM), PAC therapy) was performed on patients with ovarian cancer. Urinastatin (US) was concurrently administered to assess its effectiveness in preventing CDDP-induced nephrotoxicity. Twenty-two patients with gynecological malignant tumor were treated with PAC therapy, and of these, twelve concurrently received US. The ten who did not receive US served as the control. As a rule, one course of PAC therapy consisted of 50mg/m2 CDDP, 50mg/m2 ADM and 500mg/m2 CPM. Before the administration of CDDP, US 100,000 units was administered by I.V. drip infusion and after the administration, US 400,000 units was again administered by I.V. drip infusion at a speed of 100,000 to 200,000 units/hour. A total of approximately 3,500ml of fluids was administered I.V.. Each course of PAC therapy took 7 to 14 hours to complete. The control group underwent PAC therapy in a regimen not including US. As indexes of nephrotoxicity, serum levels of BUN, creatinine (Cr), and creatinine clearance (Ccr), and N-acetyl-beta-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP), and arylamidase (AA) activity in the urine was determined before treatment and at days 1, 2, 3, 7, 14, and 21 after the initiation of PAC therapy. Changes in serum BUN, Cr, and Ccr levels after CDDP administration in the group with and the group without concurrent US were similar. Urinary gamma-GTP, AA, and NAG activity remained unchanged after CDDP administration in the group with concurrent US. In contrast, in the group without US, this urinary enzyme activity was transiently increased after CDDP administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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