Long-term evaluation of Ifosfamide-related nephrotoxicity in children.

PURPOSE: Ifosfamide is widely used in pediatric oncology but its nephrotoxicity may become a significant issue in survivors. This study is aimed at evaluating the incidence of late renal toxicity of ifosfamide and its risk factors. PATIENTS AND METHODS: Of the 183 patients prospectively investigated for renal function, 77 treated for rhabdomyosarcoma, 39 for other soft tissue sarcoma, 39 for Ewing's sarcoma, and 28 for osteosarcoma were investigated at least 5 years after treatment. No patients had received cisplatin and/or carboplatin. Glomerular and tubular functions were graded according to the Skinner system. RESULTS: The median dose of ifosfamide was 54 g/m(2) (range, 18 to 117 g/m(2)). After a median follow-up of 10 years, 89.5% of patients had normal tubular function, and 78.5% had normal glomerular function rate (GFR). Serum bicarbonate and calcium were normal in all patients. Hypomagnesemia was observed in 1.2% and hypophosphatemia in 1%. The tubular threshold for phosphate was reduced in 24% of the patients (grade 1 in 15%, grade 2 in 8%, and grade 3 in 0.5%). Glycosuria was detected in 37% of the patients but was more than 0.5 g/24 hours in only 5%. Proteinuria was observed in 12%. Ifosfamide dose and interval from therapy to investigations were predictors of tubulopathy in univariate and multivariate analysis. In a multivariate analysis, an older age at diagnosis and the length of interval since treatment had independent impacts on the risk of abnormal GFR. CONCLUSION: Renal toxicity is moderate with a moderate dose of ifosfamide. However, since it can be permanent and can get worse with time, repeated long-term evaluations are important, and this risk should be balanced against efficacy.

Testicular function of survivors of childhood cancer: a comparative study between ifosfamide- and cyclophosphamide-based regimens.

PURPOSE: This study aimed at comparing gonadal toxicity of ifosfamide versus cyclophosphamide received during childhood. METHODS: The evaluation was based on basal FSH measurement. LH and testosterone were also measured in most of the patients. One hundred patients had received ifosfamide and 59 had received cyclophosphamide. RESULTS: Median age at treatment was 11.2 years. The median interval since treatment was 10.7 years (range 4.1-20.2) and median age at evaluation was 21.4 years (17.5-36.1). The median dose of ifosfamide and of cyclophosphamide was 54 g/m(2) (18-114) and 8.3 g/m(2) (4.6-22), respectively. All but two males had normal testosterone levels. FSH was abnormal in 28/59 patients (47.5%) after receiving cyclophosphamide and was within the normal range in 94/100 patients (94%) after receiving ifosfamide. CONCLUSIONS: These results show that ifosfamide is associated with a lower risk of gonadal damage than cyclophosphamide. The risk of abnormal FSH increased with the cumulative dose of cyclophosphamide.