Kantonsspital St.Gallen
login

Simulation-Based Assessment of the Impact of Non-Adherence on Endoxifen Target Attainment in Different Tamoxifen Dosing Strategies

Anna Mueller-Schoell, Lena Klopp-Schulze, Robin Michelet, Madelé Van Dyk, Thomas E Mürdter, Matthias Schwab, Markus Joerger, Wilhelm Huisinga, Gerd Mikus & Charlotte Kloft

abstract Tamoxifen is widely used in breast cancer treatment and minimum steady-state concentrations of its active metabolite endoxifen (C) above 5.97 ng/mL have been associated with favourable disease outcome. Yet, about 20% of patients do not reach target C applying conventional tamoxifen dosing. Moreover, 4-75% of patients are non-adherent, resulting in worse disease outcomes. Assuming complete adherence, we previously showed model-informed precision dosing (MIPD) to be superior to conventional and -guided dosing in minimising the proportion of patients with subtarget C. Given the high non-adherence rate in long-term tamoxifen therapy, this study investigated the impact of non-adherence on C target attainment in different dosing strategies. We show that MIPD allows to account for the expected level of non-adherence (here: up to 2 missed doses/week): increasing the MIPD target threshold from 5.97 ng/mL to 9 ng/mL (the lowest reported C in normal metabolisers) as a safeguard resulted in the lowest interindividual variability and proportion of patients with subtarget C even in non-adherent patients. This is a significant improvement to conventional and -guided dosing. Adding a fixed increment to the originally selected dose is not recommended, since it inflates interindividual variability.
   
citation Mueller-Schoell A, Klopp-Schulze L, Michelet R, Van Dyk M, Mürdter T E, Schwab M, Joerger M, Huisinga W, Mikus G, Kloft C. Simulation-Based Assessment of the Impact of Non-Adherence on Endoxifen Target Attainment in Different Tamoxifen Dosing Strategies. Pharmaceuticals (Basel) 2021; 14:.
   
type journal paper/review (English)
date of publishing 03-02-2021
journal title Pharmaceuticals (Basel) (14/2)
ISSN print 1424-8247
PubMed 33546125
DOI 10.3390/ph14020115