Risk factors for nephrotoxicity after ifosfamide treatment in children: a UKCCSG Late Effects Group study

The aim of this multicentre study was to document the nephrotoxicity associ ated with ifosfamide and evaluate risk factors in 148 children and young pe ople with sarcomas who underwent investigation of renal function on one occ asion each, at a median of 6 (range 1-47) months after completion of ifosfa mide (median dose 62.0 (range 6.1-165.0) g/m(2)). Investigations included g lomerular filtration rate (GFR), serum bicarbonate (HCO,) and phosphate (PO ,), and renal tubular threshold for phosphate (Tm-p/GFR). A clinically rele vant 'nephrotoxicity score' was derived. GFR was < 90 ml/min/1.73 m(2) in 6 1 of 123 evaluable patients, Tm-p/GFR < 0.9-1.1 mmol/l (age-dependent) in 4 5/103, serum PO4 < 0.9-1.mmol/l (age-dependent) in 28/135, and serum HCO3 < 20 (< 18 in infants) mmol/l in 22/95. Of 76 fully evaluable patients: 50% had mild, 20% moderate and 8% severe nephrotoxicity. Higher total ifosfamid e dose correlated significantly with greater glomerular and tubular toxicit y (P < 0.01); other risk factors, including age at treatment, demonstrated no consistent significant independent effect. Chronic ifosfamide-related gl omerular and proximal tubular toxicity were common in this large comprehens ive study. Restriction of total ifosfamide dose to < 84 g/m(2) will reduce the frequency of, but not abolish, clinically significant nephrotoxicity, w hilst doses > 119 g/m(2) are associated with a very high risk of severe tox icity. (C) 2000 Cancer Research Campaign.