| Autor: |
de Jong, Robert S., de Vries, Elisabeth G. E., Meijer, Sytze, de Jong, Paul E., Mulder, Nanno H. |
| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jun1998, Vol. 42 Issue 2, p160-164, 5p |
| Abstrakt: |
Purpose: Fostriecin is an inhibitor of topoisomerase II catalytic activity. In a phase I trial we observed renal toxicity, documented as a rise in serum creatinine, which was reversible and non-dose-limiting. The purpose of this study was a detailed analysis of this toxicity. Methods: A total of 20 patients received fostriecin as a 1-h i.v. infusion daily × 5 at doses ranging from 2 to 20 mg/m2 per day. Serum creatinine determination and urinalysis were performed daily during drug administration. Renal hemodynamics were measured by means of clearance studies using 125I-iothalamate and 131I-hippuran in eight patients at doses of ≥4 mg/m2 per day at baseline, on day 3 or 4 during the first course, and 3 weeks after the second course. Results: The rise in serum creatinine was maximal after one to two doses despite continued administration. This increase showed no correlation with the dose level at fostriecin doses of ≥4 mg/m2 per day. Urinary β2-microglobulin concentrations increased 150-fold (median), which is compatible with impaired tubular reabsorption. The median change in the glomerular filtration rate (GFR) was −36% (range −28% to −44%), that in effective renal plasma flow (ERPF) was −23% (range −11% to −36%), and the filtration fraction (FF) decreased in all patients during the first course of treatment. The values measured 3 weeks after the second course, however, did not differ from baseline. Conclusions: Fostriecin induces reversible renal hemodynamic changes compatible with renal tubular damage. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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