Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.

A prospective evaluation of high-dose ifosfamide (IFO)-related nephrotoxicity in adults and young adults previously treated with cisplatin, methotrexate (MTX) and standard-dose IFO was performed. Eighteen patients (median age 22) with recurrent osteosarcoma were studied: 11 were pretreated with MTX, cisplatin and standard-dose IFO, and seven with MTX and cisplatin. The treatment was comprised of four cycles of high-dose IFO (15 g/m2 over 5 days CI) and mesna at equivalent dose with granulocyte colony stimulating factor support. Renal function was assessed before treatment, after each IFO cycle and after chemotherapy completion. Acute nephrotubular damage was always observed after each IFO cycle with significant changes of renal tubular enzymes N-acetyl-beta-D-glucosaminidase, alanine aminipeptidase, urinary excretion and reduction of tubular reabsorption of phosphate. The appearance of glycosuria was related to the cumulative dose received. Transient and reversible renal tubular acidosis was observed in three patients. WHO grade I renal toxicity was observed in two patients. After chemotherapy completion, persistent mild glomerular and nephrotubular impairment was observed in one patient who had also received aminoglycoside antibiotics due to febrile neutropenia. Persistent and mild glycosuria was documented in another patient. No significant changes compared to baseline values were observed in the remaining patients. We conclude that a chemotherapy regimen with high-dose IFO in young adults pretreated with MTX, cisplatin and standard-dose IFO is feasible with a mild, usually reversible, nephrotoxicity.