title: Pharmacokinetically guided dosing of carboplatin in paediatric cancer patients with bilateral nephrectomy.
abstract: An approach to carboplatin dosing in children with bilateral nephrectomy using a renal function-based dosing formula with a glomerular filtration rate of zero was investigated in the current study. Carboplatin exposure was determined in a total of nine courses of chemotherapy in four patients with Wilms' tumour. Carboplatin exposures following initial dosing were less than 50% of the defined target area under the plasma concentration-time curve (AUC) in all four patients studied, with actual AUC values of between 31% and 45% of the target exposures. The use of real-time pharmacokinetic monitoring to guide dosing within a course of carboplatin treatment resulted in exposures within 15% of the target AUC in all patients. Using this information to guide dosing on additional courses of treatment in the same patient resulted in consistent exposures without the need for further monitoring or dose adjustment. These results indicate that real-time pharmacokinetic monitoring of carboplatin treatment plays a key role in ensuring that an appropriate exposure to carboplatin is achieved in children with bilateral nephrectomy. Carboplatin dosing based on patient body weight, or use of a fixed dose of carboplatin, would both be predicted to result in individual patients receiving unsatisfactory drug exposures. Further studies are warranted to further elucidate the relationship between non-renal clearance of carboplatin and patient body weight in this and other patient subpopulations where there remains concern about the optimal way to use this anticancer drug.
authors.affiliation: Northern Institute for Cancer Research, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, UK. g.j.veal@newcastle.ac.uk
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Veal
authors.forename: Martin W
authors.initials: MW
authors.lastname: English
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
authors.forename: Cay
authors.initials: C
authors.lastname: Shakespeare
authors.forename: Adam
authors.initials: A
authors.lastname: Glaser
authors.forename: Fiona
authors.initials: F
authors.lastname: Waters
authors.forename: Vicky
authors.initials: V
authors.lastname: Holden
authors.forename: Anne
authors.initials: A
authors.lastname: O'Meara
authors.forename: Antony
authors.initials: A
authors.lastname: Michalski
authors.forename: Karen
authors.initials: K
authors.lastname: Howe
authors.forename: Sue
authors.initials: S
authors.lastname: Cole
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage*; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007223:Infant; D007677:Kidney Function Tests; D008297:Male; D009392:Nephrectomy; D009396:Wilms Tumor / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin