Therapeutic drug monitoring for the individualization of docetaxel dosing: A randomized pharmacokinetic study
Purpose: 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 PKguided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel dosing on interindividual variability in exposure. Experimental Design: 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.
|Persistent URL||dx.doi.org/10.1158/1078-0432.CCR-10-1636, hdl.handle.net/1765/31703|
Engels, F.K., Loos, W.J., van der Bol, J.M., de Bruijn, P., Mathijssen, A.H.J., Verweij, J., & Mathot, R.A.A.. (2011). Therapeutic drug monitoring for the individualization of docetaxel dosing: A randomized pharmacokinetic study. Clinical Cancer Research, 17(2), 353–362. doi:10.1158/1078-0432.CCR-10-1636