Daw Najat C, Gregornik David, Rodman John, Marina Neyssa, Wu Jianrong, Kun Larry E, Jenkins Jesse J, McPherson Valerie, Wilimas Judith, Jones Deborah P
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Eur J Cancer. 2009 Jan;45(1):99-106. doi: 10.1016/j.ejca.2008.09.017. Epub 2008 Nov 6.
We prospectively evaluated tumour response and renal function in 12 newly diagnosed children with high-risk Wilms tumour receiving ifosfamide, carboplatin and etoposide (ICE) chemotherapy. Two cycles of ICE were followed by 5 weeks of vincristine, dactinomycin and doxorubicin (Adriamycin) (VDA), and nephrectomy, radiotherapy, additional VDA, and a third ICE cycle. Carboplatin dosage was based on glomerular filtration rate (GFR) to achieve targeted systemic exposure (6mg/ml min). Mean GFR (measured by technetium 99m-DTPA clearance) declined by 7% after 2 cycles of ICE and by 38% after nephrectomy; the mean carboplatin dose was reduced 32% after nephrectomy. Mean GFR remained stable after the third ICE cycle. Although urinary beta(2)-microglobulin excretion increased during therapy, no patient had clinically significant renal tubular dysfunction at the end of treatment. Treatment with ICE, nephrectomy and radiotherapy significantly reduces GFR, largely as the result of nephrectomy. Adjustment of carboplatin dosage on the basis of GFR and careful monitoring of renal function may alleviate nephrotoxicity.
我们前瞻性评估了12例新诊断的高危肾母细胞瘤患儿接受异环磷酰胺、卡铂和依托泊苷(ICE)化疗时的肿瘤反应和肾功能。两个周期的ICE化疗后,接着进行5周的长春新碱、放线菌素D和多柔比星(阿霉素)(VDA)化疗,然后进行肾切除术、放疗、额外的VDA化疗以及第三个ICE周期。卡铂剂量根据肾小球滤过率(GFR)进行调整,以达到靶向全身暴露(6mg/ml·min)。平均GFR(通过锝99m - DTPA清除率测量)在两个周期的ICE化疗后下降了7%,肾切除术后下降了38%;肾切除术后平均卡铂剂量降低了32%。第三个ICE周期后平均GFR保持稳定。虽然治疗期间尿β2 -微球蛋白排泄增加,但治疗结束时没有患者出现临床上显著的肾小管功能障碍。ICE化疗、肾切除术和放疗会显著降低GFR,主要是肾切除术的结果。根据GFR调整卡铂剂量并仔细监测肾功能可能会减轻肾毒性。