THE INFLUENCE OF SHORT VERSUS CONTINUOUS IFOSFAMIDE INFUSION ON THE DEVELOPMENT OF RENAL TUBULAR IMPAIRMENT

Ifosfamide-induced nephrotoxicity is associated with the cumulative do se given, concomitant therapy with platinum compounds, and reduction i n kidney mass. Since the ifosfamide infusion time in the treatment str ategies for both Ewing and soft tissue sarcoma was changed from 48 hr to three l-hr infusions, with otherwise unchanged dosing and administr ation, frequency and severity of ifosfamide-induced nephrotoxicity cou ld be compared between these two modalities of scheduling. The study p opulation consisted of 51 patients, 23 after continous and 28 after sh ort infusion of ifosfamide. Mean observation time for patients after c ontinuous infusion was 4.5 years and for patients after short infusion 1.5 years. Renal function was assessed by measuring proximal tubular solute handling (phosphate, glucose, 16 amino acids and sodium); in ad dition, creatinine clearance and serum bicarbonate levels were recorde d. Two patients of the continuous infusion group developed renal Fanco ni syndrome, and another two a generalized, but subclinical, tubulopat hy. In contrast, Fanconi syndrome was not observed after short infusio n, and there was only one patient with a generalized subclinical tubul opathy. Among the individual parameters examined, impairment of amino acid reabsorption was seen most frequently (78% versus 57%, comparing continuous versus short infusion). All these differences did, however, not yield statistical significance. Confining this analysis to the fi rst 18 months off therapy again disclosed no differences in frequency and severity of renal impairment. Ifosfamide-induced nephrotoxicity do es not appear to be significantly related to its schedule of applicati on A possible influence of the cumulative mesna dose on the developmen t of this side effect is discussed.