TY - JOUR
T1 - Individualized dosing of oral targeted therapies in oncology is crucial in the era of precision medicine
AU - Groenland, Stefanie L.
AU - Mathijssen, Ron H.J.
AU - Beijnen, Jos H.
AU - Huitema, Alwin D.R.
AU - Steeghs, Neeltje
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - Individualized dosing
KW - Oral targeted therapies
KW - Personalized medicine
KW - Precision medicine
KW - Therapeutic drug monitoring
UR - http://www.scopus.com/inward/record.url?scp=85067296683&partnerID=8YFLogxK
U2 - 10.1007/s00228-019-02704-2
DO - 10.1007/s00228-019-02704-2
M3 - Review article
C2 - 31175385
AN - SCOPUS:85067296683
SN - 0031-6970
VL - 75
SP - 1309
EP - 1318
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
IS - 9
ER -