4.P.34 RENAL TOXICITY IN PATIENTS WITH EWINGS SARCOMA/PNET TREATED WITH HIGH DOSES OF IFOSFAMIDE

Abstract

Introduction: Late effects of treatment in pediatric oncology patients are major issues of follow up care. Success in overall survival of patients with Ewing’s sarcoma/PNET (ES/PNET) correlates with cumulative doses of alkylating agents especially. Renal toxicity is subject of interest due to irreversible tubulopathy and need of many concomitant nephrotoxic drugs given during treatment.

Objectivee: Patients suffered from ES/PNET on Euro Ewing 99 protocol were eligible for evaluation of renal functions during therapy and follow up.

Methods: Design ofthis study was single institution observational. Total of 20 patients were included 9 females and 11 males. Renal toxicity was assessed as glomerular filtration rate according to Schwartz’s formula (GFR), serum creatinine (S-crea), fractionated phosphate reabsorption (Tp/Ccrea), daily phosphate waste in urine (U-P), daily protein waste in urine (U-Pr) and minimal signs of Fanconi syndrome (FS; positive urine glucose and/or protein).

Results: Median age at time of diagnosis was 11.7 years. Median follow up from time of diagnosis was 1.2 months. Median dose of ifosfamide was 87 g/ m2. Median GFR decreased from 2.7ml/s to 2.2 ml/s (p=0.001). Median of S-crea was initially 48 μl/l and 58.1 μl/l at time of last follow up (p< 0.001). Median of Tp/Ccrea was 1.2 mmol/l and decreased to 1.1 mmol/ l at the end of treatment (p= 0.026). U-P was initially and finally 11.9 mmol and 25.1mmol, respectively (p = 0.008). Median of tubular reabsorption of phosphate decreased from 95% initially to 90% (p=0.001). Daily waste of protein increased from 0.11 g to 0.43 g (p= 0.051). Minimal signs of FS developed in 9 of 17 patients (53%).

Conclsions: Patients with high cumulative doses of ifosfamide are at risk of renal impairement. Despite statistically significant differences of severeral measures observed in this study, clinical impact of post treatment values does not exceed grade 1 toxicity. Observation of minimal signs of FS developed in 53% of patients is of concern and further treatment of ES/PNET should be carefully focused on late effect too.