Tamoxifen Metabolism and the Impact of Tamoxifen Dose on the Level of the Active Metabolites in Endocrine Sensitive Breast Cancer Patients
- To determine how the increase of tamoxifen citrate dose influences the level of its
major metabolites in patients with hormone-sensitive breast cancer.
- To characterize the population pharmacokinetic profile
- To investigate the role of the other CYPs
- To assess the relation between clinical symptoms and CYP2D6 genotypes and/or active
- To explore the correlation between genotypes/metabolites levels and clinical outcomes
in terms of tumor relapse.
- To assess the feasibility, efficacy, and safety of concentration-guided adjustment of
tamoxifen citrate dosage.
- To conduct other exploratory analysis based on the eventual new data coming up in the
OUTLINE: Patients receive oral tamoxifen citrate (at a dose of 40 mg/day) daily for 4 months
in the absence of disease progression or unacceptable toxicity.
Blood samples are collected for PK, genotyping, phenotyping, and further analysis.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determination of CYP2D6 genotype and determination of plasma concentrations of tamoxifen citrate and its metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and endoxifen) under the 20 mg daily and 40 mg daily schedules
Khalil Zaman, MD
Centre Hospitalier Universitaire Vaudois