Renal function following combination chemotherapy with ifosfamide and cisplatin in patients with osteogenic sarcoma

Ifosfamide and cisplatin are active agents that are currently used in the treatment of osteosarcoma. Nephrotoxicity has been reported following their use in combination and alone. This study evaluates renal function in children and adolescents (median age 16 years) at least 3 months following completion of a chemotherapy regimen which included 54 g/m2 ifosfamide, 360 mg/m2 cisplatin, doxorubicin, and high-dose methotrexate.

Mean glomerular filtration rate (GFR) was determined by inulin or iothalamate clearance; proximal tubular function was evaluated by measuring fractional excretion of glucose (FEglu), tubular maximum phosphate reabsorption per GFR (TMP/GFR), FE of urate, and 24-hour amino acid excretion. Distal tubular function was evaluated by 24-hour urinary calcium, FE of magnesium, and urinary osmolality after water deprivation. Twenty-four-hour urinary protein excretion was measured.

The mean GFR was 97 ml/min/1.73 m2. Although 10 of 24 patients had GFRs lower than normal, the lowest value was only 22% below the lower limit of normal and would not account for any clinical compromise. Proximal tubular function evaluation revealed normal FEglu, normal mean TMP/GFR values, and high FE of urate (1 5.7%). Two of twenty-four patients were shown to have mild generalized aminoaciduria. Distal tubular function evaluation showed normal 24-hour urinary calcium levels (mean 3.4 mg/kg) and FE of magnesium as well as normal urinary osmolality. Twenty-four-hour urinary protein excretion was normal in all patients.

The lack of clinically significant renal abnormalities observed in patients who received combination chemotherapy with ifosfamide and cisplatin for osteosarcoma is encouraging for future osteosarcoma protocol development.