TY - JOUR
T1 - Reasons for non-feasibility of therapeutic drug monitoring of oral targeted therapies in oncology - an analysis of the closed cohorts of a multicentre prospective study
AU - van der Kleij, Maud B A
AU - Guchelaar, Niels A D
AU - Meertens, Marinda
AU - Westerdijk, Kim
AU - Giraud, Eline L
AU - Bleckman, Roos F
AU - Groenland, Stefanie L
AU - van Eerden, Ruben A G
AU - Imholz, Alex L T
AU - Vulink, Annelie J E
AU - Otten, Hans-Martin
AU - Fiebrich-Westra, Helle-Brit
AU - Lubberman, Floor J E
AU - Desar, Ingrid M E
AU - Moes, Dirk-Jan A R
AU - Touw, Daan J
AU - Koolen, Stijn L W
AU - Gelderblom, Hans
AU - Reyners, An K L
AU - van Erp, Nielka P
AU - Mathijssen, Ron H J
AU - Huitema, Alwin D R
AU - Steeghs, Neeltje
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9
Y1 - 2024/9
N2 - BACKGROUND: Therapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.METHODS: We evaluated drug cohorts from the Dutch Pharmacology Oncology Group - TDM study. Based on PK levels taken at pre-specified time points, PK-guided interventions were performed. Feasibility of TDM was evaluated, and based on the success and practicability of TDM, cohorts could be closed.RESULTS: For 10 out of 24 cohorts TDM was not feasible and inclusion was closed. A high incidence of adverse events resulted in closing the cabozantinib, dabrafenib/trametinib, everolimus, regorafenib and vismodegib cohort. The enzalutamide and erlotinib cohorts were closed because almost all PK levels were above target. Other, non-pharmacological reasons led to closing the palbociclib, olaparib and tamoxifen cohort.CONCLUSIONS: Although TDM could help personalising treatment for many drugs, the above-mentioned reasons can influence its feasibility, usefulness and clinical applicability. Therefore, routine TDM is not advised for cabozantinib, dabrafenib/trametinib, enzalutamide, erlotinib, everolimus, regorafenib and vismodegib. Nonetheless, TDM remains valuable for individual clinical decisions.
AB - BACKGROUND: Therapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.METHODS: We evaluated drug cohorts from the Dutch Pharmacology Oncology Group - TDM study. Based on PK levels taken at pre-specified time points, PK-guided interventions were performed. Feasibility of TDM was evaluated, and based on the success and practicability of TDM, cohorts could be closed.RESULTS: For 10 out of 24 cohorts TDM was not feasible and inclusion was closed. A high incidence of adverse events resulted in closing the cabozantinib, dabrafenib/trametinib, everolimus, regorafenib and vismodegib cohort. The enzalutamide and erlotinib cohorts were closed because almost all PK levels were above target. Other, non-pharmacological reasons led to closing the palbociclib, olaparib and tamoxifen cohort.CONCLUSIONS: Although TDM could help personalising treatment for many drugs, the above-mentioned reasons can influence its feasibility, usefulness and clinical applicability. Therefore, routine TDM is not advised for cabozantinib, dabrafenib/trametinib, enzalutamide, erlotinib, everolimus, regorafenib and vismodegib. Nonetheless, TDM remains valuable for individual clinical decisions.
UR - http://www.scopus.com/inward/record.url?scp=85201514436&partnerID=8YFLogxK
U2 - 10.1038/s41416-024-02789-2
DO - 10.1038/s41416-024-02789-2
M3 - Article
C2 - 38971952
SN - 0007-0920
VL - 131
SP - 843
EP - 851
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -