title: Flat dosing of carboplatin is justified in adult patients with normal renal function.
abstract: OBJECTIVE
  The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance. Substitution of the GFR in this formula by an estimate of creatinine clearance or GFR as calculated by formulae using serum creatinine (SCR; Cockcroft-Gault, Jelliffe, and Wright) is, however, routine clinical practice in many hospitals. The goal of this study was to validate this practice retrospectively in a large heterogeneous adult patient population.
  
  
  METHODS
  Concentration-time data of ultrafilterable platinum of 178 patients (280 courses, 3,119 samples) with different types of cancer receiving carboplatin-based chemotherapy in conventional and high doses were available. Data were described with a linear two-compartment population pharmacokinetic model. Relations between SCR-based formulae for estimating renal function and carboplatin clearance were investigated.
  
  
  RESULTS
  None of the tested SCR-based estimates of renal function were relevantly related to the pharmacokinetic variables of carboplatin. Neither SCR (median, 51; range, 18-124 micromol/L) nor the estimated GFR using the three different formulae was related to carboplatin clearance.
  
  
  CONCLUSIONS
  Our data do not support the application of modifications of the Calvert formula by estimating GFR from SCR in the a priori dosing of carboplatin in patients with relatively normal renal function (creatinine clearance, >50 mL/min). For targeted carboplatin exposures, the original Calvert formula, measuring GFR using the 51Cr-EDTA clearance, remains the method of choice. Alternatively, in patients with normal renal function, a flat dose based on the mean population carboplatin clearance should be administered.
authors.affiliation: Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, and Faculty of Pharmaceutical Sciences, Utrecht University, the Netherlands. apcek@slz.nl
authors.forename: Corine
authors.initials: C
authors.lastname: Ekhart
authors.forename: Milly E
authors.initials: ME
authors.lastname: de Jonge
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin