Tamoxifen Prediction Study in Patients With ER+ Breast Cancer
Status:
Not yet recruiting
Trial end date:
2023-07-01
Target enrollment:
Participant gender:
Summary
Adjuvant treatment with tamoxifen is the standard of care for women with estrogen receptor
positive (ER+) breast cancer. Tamoxifen is converted to endoxifen, its active metabolite, via
CYP2D6 enzymes. The literature states that an endoxifen concentration of at least 16 nmol/L
is needed to produce a therapeutic effect (4). Therapeutic Drug Monitoring (TDM) has been
proven to be a successful technique to reach the 16 nmol/L endoxifen threshold after 6
months. However, in general TDM can only be used when a drug is in steady-state, which for
endoxifen is reached after 3 months for normal metabolizers. For poor- and intermediate
metabolizers, the time until steady-state is presumably even longer. This could possibly
result in undertreatment within the first 3 to 6 months of tamoxifen treatment. In this
study, model-informed precision dosing (MIPD) will be used to counter this problem. The
Pharmacokinetic-model, which is used for MIPD, includes CYP2D6 genotype, co-medication, age,
body height, BMI and CYP2D6/CYP3A inhibitor use to predict a patient tailored dose. Using
MIPD, our aim is to decrease the proportion of patients that are undertreated within the
first three months of tamoxifen treatment.