Skinner R, Pearson A D, English M W, Price L, Wyllie R A, Coulthard M G, Craft A W
Sir James Spence Institute of Child Health, University of Newcastle upon Tyne, Royal Victoria Infirmary, UK.
Lancet. 1996 Aug 31;348(9027):578-80. doi: 10.1016/s0140-6736(96)03480-0.
Risk factors for long-term nephrotoxicity after ifosfamide for childhood cancers are not fully known. We have studied patient-related and treatment-related risk factors for chronic ifosfamide nephrotoxicity.
A group of 23 children who had received ifosfamide at age 2.1-16.2 years (median 6.9) for various cancers were assessed for nephrotoxicity, at 1-28 (2) months after the end of treatment, by renal function testing, laboratory values, and a grading score (none, mild, moderate, severe). No patient had received cisplatin or undergone nephrectomy. 13 children were reassessed at 10-26 (23) months; eight had died and two were not evaluable. The median total ifosfamide dose was 100.8 (9.0-160.4) g/m2 over a median of 15 courses every 3 weeks as a 48-72 h continuous intravenous infusion (in 22 cases), with mesna and hydration.
Glomerular filtration rate was below normal in ten (45%) of 22 evaluable children; their rate was 61-85 mL/min per 1.73 m2. Proximal tubular toxicity led to hypophosphataemic rickets and/or renal tubular acidosis in six children, and distal tubular toxicity caused nephrogenic diabetes insipidus in one. Of the risk factors analysed by multiple regression, only total ifosfamide dose was associated with proximal tubular toxicity. Only two of ten evaluable patients who received under 100 g/m2 developed moderate nephrotoxicity, whereas six of ten who received over this dose had moderate or severe nephrotoxicity.
High total ifosfamide dose was the only risk factor we identified. Although inter-patient variability was high, cumulative doses of 100 g/m2 or higher should be avoided in children with cancer.
对于儿童癌症患者使用异环磷酰胺后发生长期肾毒性的危险因素尚不完全清楚。我们研究了与患者相关和与治疗相关的慢性异环磷酰胺肾毒性危险因素。
对一组23名年龄在2.1 - 16.2岁（中位数6.9岁）因各种癌症接受异环磷酰胺治疗的儿童，在治疗结束后1 - 28（中位数2）个月通过肾功能测试、实验室检查值和分级评分（无、轻度、中度、重度）评估肾毒性。所有患者均未接受顺铂治疗或行肾切除术。13名儿童在10 - 26（中位数23）个月时接受了重新评估；8名儿童死亡，2名儿童无法评估。异环磷酰胺总剂量中位数为100.8（9.0 - 160.4）g/m²，每3周进行15个疗程的治疗，中位数为48 - 72小时持续静脉输注（22例），同时给予美司钠和水化治疗。
22名可评估儿童中有10名（45%）肾小球滤过率低于正常；其肾小球滤过率为61 - 85 mL/min/1.73 m²。近端肾小管毒性导致6名儿童出现低磷性佝偻病和/或肾小管酸中毒，远端肾小管毒性导致1名儿童出现肾性尿崩症。在通过多元回归分析的危险因素中，只有异环磷酰胺总剂量与近端肾小管毒性相关。在接受低于100 g/m²的10名可评估患者中，只有2名出现中度肾毒性，而接受超过此剂量的10名患者中有6名出现中度或重度肾毒性。
异环磷酰胺总剂量高是我们确定的唯一危险因素。尽管患者间变异性很大，但癌症儿童应避免累积剂量达到100 g/m²或更高。
