Integrated Data Analysis of Six Clinical Studies Points Toward Model-Informed Precision Dosing of Tamoxifen.

ABSTRACT:

Introduction

At tamoxifen standard dosing, ∼20% of breast cancer patients do not reach proposed target endoxifen concentrations >5.97 ng/mL. Thus, better understanding the large interindividual variability in tamoxifen pharmacokinetics (PK) is crucial. By applying non-linear mixed-effects (NLME) modeling to a pooled 'real-world' clinical PK database, we aimed to (i) dissect several levels of variability and identify factors predictive for endoxifen exposure and (ii) assess different tamoxifen dosing strategies for their potential to increase the number of patients reaching target endoxifen concentrations.

Methods

Tamoxifen and endoxifen concentrations with genetic and demographic data of 468 breast cancer patients from six reported studies were used to develop a NLME parent-

SUBMITTER: Klopp-Schulze L 

PROVIDER: S-EPMC7136483 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature