What we do
About our project
Rationale
Adjuvant treatment with tamoxifen significantly reduces the chance of recurrence. Despite the adjuvant endocrine treatment, in some patients the disease returns within five years. Literature indicates that there is a minimal endoxifen concentration of 16 nmol/L to produce a therapeutic effect. In this exploratory study we will therefore evaluate the impact of TDM guided dosing on endoxifen levels in patients treated with tamoxifen.
Objective
The primary objective is to prove that Therapeutic Drug Monitoring of tamoxifen is feasible in clinical practice.
Therapeutic Drug Monitoring
As a prodrug, tamoxifen is susceptible to metabolism by the cytochrome P450 enzyme system. The most active metabolite created in this process is endoxifen. Literature indicates that a minimal endoxifen concentration of 16 nmol/L is needed to produce a therapeutic effect. Endoxifen concentrations are measured throughout the course of treatment after which the tamoxifen dose is adapted in patients with concentrations below the threshold. This approach is called Therapeutic Drug Monitoring (TDM).Main study parameters/endpoints
The primary outcome parameter is the percentage of patients with endoxifen levels ≥16 nmol/L at 6 months after start of treatment with tamoxifen.Our research focus
Study objectives
- To prove that TDM of tamoxifen is feasible in clinical practice
- To determine the relation between the pharmacokinetics of tamoxifen and its metabolites
Collaborations
Collaborations within Erasmus MC
- Prof. Dr. C. de Uyl-de Groot, Professor of Health Technology Assessment (HTA), Erasmus school of Health Policy & Management, Erasmus University Rotterdam
- Dr. R.J. de Knegt, MD, PhD, Erasmus Medical Center, Department of Gastroenterology & Hepatology
Publications
Madlensky, L et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011;89(5):718-25.
Our team
- Prof. Dr. Ron H.J. Mathijssen, principal investigator
- Louwrens Braal, PhD candidate
- Dr. Agnes Jager, researcher
- Dr. Stijn L.W. Koolen, principal investigator
