TY - JOUR
T1 - Long-term evaluation of ifosfamide-related nephrotoxicity in children
AU - Oberlin, Odile
AU - Fawaz, Oumaya
AU - Rey, Annie
AU - Niaudet, Patrick
AU - Ridola, Vita
AU - Orbach, Daniel
AU - Bergeron, Christophe
AU - Defachelles, Annie Sophie
AU - Gentet, Jean Claude
AU - Schmitt, Claudine
AU - Rubie, Hervé
AU - Munzer, Martine
AU - Plantaz, Dominique
AU - Deville, Anne
AU - Minard, Veronique
AU - Corradini, Nadège
AU - Leverger, Guy
AU - De Vathaire, Florent
PY - 2009/11/10
Y1 - 2009/11/10
N2 - 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/m2 (range, 18 to 117 g/m2). 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.
AB - 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/m2 (range, 18 to 117 g/m2). 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.
UR - http://www.scopus.com/inward/record.url?scp=73949098182&partnerID=8YFLogxK
U2 - 10.1200/JCO.2008.17.5257
DO - 10.1200/JCO.2008.17.5257
M3 - Article
C2 - 19826134
AN - SCOPUS:73949098182
SN - 0732-183X
VL - 27
SP - 5350
EP - 5355
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 32
ER -