Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors.
OBJECTIVE
The long-term outcome of platinum-induced nephrotoxicity is unknown. This prospective single-centre longitudinal cohort study evaluated long-term changes following treatment in childhood.


METHODS
63 children treated with platinum (27 cisplatin, 24 carboplatin and 12 both) were studied at the end of treatment (End), 1 year and 10 years later. No child received ifosfamide. Glomerular filtration rate (GFR), serum calcium and magnesium (Mg) were measured, and total nephrotoxicity score (N(s)) was graded.


RESULTS
There was no significant overall change in renal function over time in any treatment group (cisplatin, carboplatin or combined). Apart from marginally reduced median GFR (84 ml/min/1.73 m(2)) and Mg (0.68 mmol/l) at End of cisplatin, median GFR, Ca and Mg were normal at all times in each group. At 10 years, GFR was <60 ml/min/1.7 3m(2) in 11%, N(s) grade was severe in 15% and oral Mg supplements were required in 7% cisplatin patients. After cisplatin, older age at treatment was correlated with lower GFR at 10 years (p=0.005), and higher N(s) at End and 10 years (both p=0.02). After carboplatin treatment, older age was associated with lower GFR at all times, and with higher N(s) at End and 1 year (all p<0.03). Higher cisplatin dose rate (>40 mg/m(2)/day) was associated with higher N(s) at 1 year (p=0.02) and higher carboplatin dose with lower Mg at 1 year and with higher N(s) at 1 and 10 years (all p<0.008).


CONCLUSIONS
Platinum nephrotoxicity did not change significantly over 10 years. Its severity was correlated to older age at treatment, and at some time points to higher cisplatin dose rate and higher cumulative carboplatin dose.
Department of Paediatric and Adolescent Oncology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK. Roderick.Skinner@ncl.ac.uk
Roderick
R
Skinner
Annie
A
Parry
Lisa
L
Price
Michael
M
Cole
Alan W
AW
Craft
Andrew D J
AD
Pearson
D000293:Adolescent; D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002118:Calcium / Q000097:blood; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D007684:Kidney Tubules / Q000187:drug effects; D008274:Magnesium / Q000097:blood; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D012720:Severity of Illness Index; D017741:Survivors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D016190:Carboplatin; D008274:Magnesium; D002945:Cisplatin; D002118:Calcium