Stöhr W, Paulides M, Bielack S, Jürgens H, Treuner J, Rossi R, Langer T, Beck J D
Department of Pediatric Oncology, LESS center, University Hospital for Children and Adolescents, Erlangen, Germany.
Pediatr Blood Cancer. 2007 Apr;48(4):447-52. doi: 10.1002/pbc.20858.
Ifosfamide is widely used in paediatric oncology, but its use is limited by nephrotoxic side effects. The aim of this study was to evaluate the incidence and risk factors of tubulopathy, with special emphasis on the influence of age, where different findings have been published so far.
Five hundred ninety three children and adolescents treated for Ewing, osteo- or soft-tissue sarcoma (median age at diagnosis: 11.7 years) were prospectively investigated for nephrotoxicity in the Late Effects Surveillance System (LESS) study. Tubulopathy was diagnosed in case of continuing hypophosphatemia and proteinuria.
After a median follow up of 19 months, 27 patients (4.6%; 95% CI: 3.0-6.6%) had newly developed tubulopathy. This incidence was 0.4% (95% CI: 0-2.4%) in patients treated with a cumulative ifosfamide dose of < or =24 g/m2, 6.5% (95% CI: 3.6-10.7%) after 24-60 g/m2, and 8.0% (95% CI: 4.2-13.6%) after > or = 60 g/m2. In multivariate analysis, children younger than 4 years at time of diagnosis had an 8.7-fold (95% CI: 3.5-21.8) higher risk for tubulopathy than older patients. Neither carboplatin treatment nor abdominal irradiation showed any significant influence.
Ifosfamide-induced nephrotoxicity was found in 4.6% of patients. Risk factors were the cumulative ifosfamide dose and young age at treatment.
异环磷酰胺广泛应用于儿童肿瘤学，但因其肾毒性副作用限制了其使用。本研究旨在评估肾小管病变的发生率及危险因素，特别强调年龄的影响，目前已有不同的研究结果发表。
在晚期效应监测系统（LESS）研究中，对593例接受尤因肉瘤、骨肉瘤或软组织肉瘤治疗的儿童和青少年（诊断时中位年龄：11.7岁）进行了肾毒性的前瞻性调查。若出现持续性低磷血症和蛋白尿，则诊断为肾小管病变。
中位随访19个月后，27例患者（4.6%；95%置信区间：3.0 - 6.6%）新发生肾小管病变。累积异环磷酰胺剂量≤24 g/m²的患者中，这一发生率为0.4%（95%置信区间：0 - 2.4%）；24 - 60 g/m²后为6.5%（95%置信区间：3.6 - 10.7%）；≥60 g/m²后为8.0%（95%置信区间：4.2 - 13.6%）。多因素分析显示，诊断时年龄小于4岁的儿童发生肾小管病变的风险比年长患者高8.7倍（95%置信区间：3.5 - 21.8）。卡铂治疗和腹部放疗均未显示出任何显著影响。
4.6%的患者出现了异环磷酰胺诱导的肾毒性。危险因素为异环磷酰胺的累积剂量和治疗时年龄较小。
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