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research-project
Research project

TOTAM

Status: Ongoing

Therapeutic Drug Monitoring guided tamoxifen dosing: a feasibility study in patients with hormone positive breast cancer

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

Publications

Madlensky, L et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011;89(5):718-25.

Our team