Renal function after ifosfamide, carboplatin and etoposide (ICE) chemotherapy, nephrectomy and radiotherapy in children with Wilms tumour

Abstract

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.

Fig 1. Therapy schema

V=vincristine 1.5 mg/m² (maximum dose, 2 mg); D=dactinomycin 0.6 mg/m² (maximum dose, 2 mg); A=doxorubicin (Adriamycin) 25 mg/m²; ICE chemotherapy: C=carboplatin, dosage based on GFR to target an AUC of 6 mg/ml × min on day 1; E=etoposide 100 mg/m² per day on days 2–4; I=ifosfamide 2 g/m² per day on days 2–4.

Fig 2

Bland-Altman plot to assess agreement between GFR and estimated creatinine clearance (n = 35 pairs). The solid line represents the bias of the difference between pairs (17.8 ml/min per 1.73 m²) and the dashed lines represent the 95% confidence interval.

Fig 3

Renal tubular function was longitudinally assessed by measuring urinary magnesium excretion (a), renal tubular threshold for phosphate (b), and urinary β₂-microglobulin (c) in patients with Wilms tumour treated with ICE. Shaded areas (a, b) represent the normal range.