Renal function after ifosfamide, carboplatin and etoposide (ICE) chemotherapy, nephrectomy and radiotherapy in children with wilms tumour
Received 4 July 2008; received in revised form 26 August 2008; accepted 25 September 2008. published online 10 November 2008.
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/mlmin). 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 β2-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.
aDepartment of Oncology, Mail Stop 260, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee, TN 38105-3678, USA
bDepartment of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
cDepartment of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
dDepartment of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
eDepartment of Radiological Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
fDepartment of Pathology and Laboratory Medicine, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
gChildren’s Foundation Research Center at LeBonheur Children’s Medical Center, Memphis, Tennessee, USA
Corresponding author: Address: Department of Oncology, Mail Stop 260, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee, TN 38105-3678, USA. Tel.: +1 901 595 2573; fax: +1 901 521 9005.
h Present address: Pediatric Hematology/Oncology, Stanford University Medical Center, Palo Alto, California, USA.