Raney B, Ensign L G, Foreman J, Khan F, Newton W, Ortega J, Ragab A, Wharam M, Wiener E, Maurer H
Rhabdomyosarcoma Study Committee of the Childrens Cancer Group, Duke University Medical Center.
Am J Pediatr Hematol Oncol. 1994 Nov;16(4):286-95.
The purpose of this review is to characterize the nephrotoxicity noted in newly diagnosed patients under 21 years of age after treatment with ifosfamide-containing chemotherapy regimens and local irradiation for localized gross residual rhabdomyosarcoma or undifferentiated sarcoma.
From 1987 to 1991, 194 previously untreated patients received vincristine and ifosfamide plus dactinomycin or etoposide for 1-2 years. Ifosfamide was given at 1.8 g/m2/day for 5 days with sodium mercaptoethane sulfonate, or 9 g/m2 of ifosfamide per course. The three-drug regimen was repeated every 3-4 weeks.
Twenty-eight patients (14%) developed renal toxicity: 19 had renal tubular dysfunction (RTD) characterized by low serum phosphate (< or = 3 mg/dl) or bicarbonate (< 20 or = mEq/L) levels, five had decreased glomerular function (DGF), and four had both RTD and DGF. When nine or more courses of ifosfamide (> 72 g/m2) were given, children < 3 years of age had a higher incidence of RTD than did children > or = 3 years of age (34% versus 6%; p < 0.001). A similar age difference was observed even when eight or fewer courses (< or = 72 g/m2) were given (p = 0.03). A matched case-control comparison showed that renal abnormalities at diagnosis, chiefly hydronephrosis, also increased the risk of renal tubular injury by ifosfamide by a factor of 13 (p < 0.001). Patients with DGF tended to be older than those with RTD, and all but one received > 72 g/m2 of ifosfamide.
Patients who are < 3 years of age who receive more than eight courses (> 72 g/m2) of ifosfamide and who have a preexisting renal abnormality have an increased risk of RTD and DGF. The renal function of patients being considered for ifosfamide treatment must be carefully monitored. Ifosfamide should be avoided in patients with renal abnormalities at diagnosis unless the potential benefit clearly exceeds the risk of further renal impairment.
本综述旨在描述21岁以下新诊断患者在接受含异环磷酰胺的化疗方案及局部放疗治疗局限性大体残留横纹肌肉瘤或未分化肉瘤后所出现的肾毒性特征。
1987年至1991年，194例既往未接受过治疗的患者接受长春新碱、异环磷酰胺加放线菌素D或依托泊苷治疗1至2年。异环磷酰胺剂量为1.8 g/m²/天，连用5天，并给予巯乙磺酸钠，或每疗程9 g/m²异环磷酰胺。每3至4周重复一次三联化疗方案。
28例患者（14%）出现肾毒性：19例出现肾小管功能障碍（RTD），表现为血清磷酸盐水平低（≤3 mg/dl）或碳酸氢盐水平低（<20 mEq/L）；5例出现肾小球功能减退（DGF）；4例同时出现RTD和DGF。当给予9个或更多疗程的异环磷酰胺（>72 g/m²）时，3岁以下儿童RTD的发生率高于3岁及以上儿童（34%对6%；p<0.001）。即使给予8个或更少疗程（≤72 g/m²），也观察到类似的年龄差异（p = 0.03）。配对病例对照比较显示，诊断时的肾脏异常（主要是肾积水）也使异环磷酰胺导致肾小管损伤的风险增加了13倍（p<0.001）。DGF患者往往比RTD患者年龄大，除1例患者外，所有患者接受的异环磷酰胺剂量均>72 g/m²。
3岁以下接受超过8个疗程（>72 g/m²）异环磷酰胺且存在肾脏异常的患者，发生RTD和DGF的风险增加。对于考虑接受异环磷酰胺治疗的患者，必须仔细监测其肾功能。诊断时存在肾脏异常的患者应避免使用异环磷酰胺，除非潜在益处明显超过进一步肾功能损害的风险。
