title: Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study.
abstract: OBJECTIVE
  Docetaxel pharmacokinetic (PK) parameters, notably clearance and exposure (AUC), are characterized by large interindividual variability. The purpose of this study was to evaluate the effect of PK-guided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel dosing on interindividual variability in exposure.
  
  
  METHODS
  A limited sampling strategy in combination with a validated population PK model, Bayesian analysis, and a predefined target AUC was used. Fifteen patients were treated for at least 2 courses with body surface area-based docetaxel and 15 with at least 1 course of PK-guided docetaxel dosing.
  
  
  RESULTS
  Interindividual variability (SD of ln AUC) was decreased by 35% (N = 15) after 1 PK-guided course; when all courses were evaluated, variability was decreased by 39% (P = 0.055). PK-guided dosing also decreased the interindividual variability of percentage decrease in white blood cell and absolute neutrophil counts by approximately 50%.
  
  
  CONCLUSIONS
  Further research is required to determine whether the decrease in PK variability can contribute to a reduction in interindividual variability in efficacy and toxicity.
authors.affiliation: Department of Medical Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands. f.engels@erasmusmc.nl
authors.forename: Frederike K
authors.initials: FK
authors.lastname: Engels
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Loos
authors.forename: Jessica M
authors.initials: JM
authors.lastname: van der Bol
authors.forename: Peter
authors.initials: P
authors.lastname: de Bruijn
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.forename: Jaap
authors.initials: J
authors.lastname: Verweij
authors.forename: Ron A A
authors.initials: RA
authors.lastname: Mathot
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D000077143:Docetaxel; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel