Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine
Purpose While in the era of precision medicine, the right drug for each patient is selected based on molecular tumor characteristics, most novel oral targeted anticancer agents are still being administered using a one-size-fits-all fixed dosing approach. In this review, we discuss the scientific evidence for dose individualization of oral targeted therapies in oncology, based on therapeutic drug monitoring (TDM).
Methods Based on literature search and our own experiences, seven criteria for drugs to be suitable candidates for TDM will be addressed: (1) absence of an easily measurable biomarker for drug effect; (2) long-term therapy; (3) availability of a validated sensitive bioanalytical method; (4) significant variability in pharmacokinetic exposure; (5) narrow therapeutic range; (6) defined and consistent exposure-response relationships; (7) feasible dose-adaptation strategies.
Results All of these requirements are met for most oral targeted therapies in oncology. Also, prospective studies have already shown TDM to be feasible for imatinib, pazopanib, sunitinib, everolimus, and endoxifen.
Conclusions In order to realize the full potential of personalized medicine in oncology, patients should not only be treated with the right drug, but also at the right dose. TDM could be a suitable tool to achieve this.
|Keywords||Therapeutic drug monitoring, Individualized dosing, Personalized medicine, Precision medicin, e Oral targeted therapies|
|Persistent URL||dx.doi.org/10.1007/s00228-019-02704-2, hdl.handle.net/1765/119464|
|Series||VSNU Open Access deal|
|Journal||European Journal of Clinical Pharmacology|
|Note||corresponding author at the Netherlands Cancer Institute|
Groenland, S.L., Mathijssen, A.H.J, Beijnen, J.H, Huitema, A.D.R, & Steeghs, N. (2019). Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine. European Journal of Clinical Pharmacology, 75(9), 1309–1318. doi:10.1007/s00228-019-02704-2