Clin Pharmacokinet. 2021 Nov 17; doi: 10.1007/s40262-021-01077-z. Epub 2021 Nov 17.

Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer.

Clinical pharmacokinetics

C Louwrens Braal, Agnes Jager, Esther Oomen-de Hoop, Justin D Westenberg, Koen M W T Lommen, Peter de Bruijn, Mijntje B Vastbinder, Quirine C van Rossum-Schornagel, Martine F Thijs-Visser, Robbert J van Alphen, Liesbeth E M Struik, Hanneke J M Zuetenhorst, Ron H J Mathijssen, Stijn L W Koolen

PMID: 34786650 DOI: 10.1007/s40262-021-01077-z

Abstract

BACKGROUND: Endoxifen is the most important active metabolite of tamoxifen. Several retrospective studies have suggested a minimal or threshold endoxifen systemic concentration of 14-16 nM is required for a lower recurrence rate. The aim of this study was to investigate the feasibility of reaching a predefined endoxifen level of ≥ 16 nM (5.97 ng/mL) over time using therapeutic drug monitoring (TDM).

METHODS: This prospective open-label intervention study enrolled patients who started treatment with a standard dose of tamoxifen 20 mg once daily for early breast cancer. An outpatient visit was combined with a TDM sample at 3, 4.5, and 6 months after initiation of the tamoxifen treatment. The tamoxifen dose was escalated to a maximum of 40 mg if patients had an endoxifen concentration < 16 nM. The primary endpoint of the study was the percentage of patients with an endoxifen level ≥ 16 nM at 6 months after the start of therapy compared with historical data, in other words, 80% of patients with endoxifen levels ≥ 16 nM with standard therapy.

RESULTS: In total, 145 patients were included. After 6 months, 89% of the patients had endoxifen levels ≥ 16 nM, compared with a literature-based 80% of patients with endoxifen levels ≥ 16 nM at baseline (95% confidence interval 82-94; P = 0.007). In patients with an affected CYP2D6 allele, it was not always feasible to reach the predefined endoxifen level of ≥ 16 nM. No increase in tamoxifen-related adverse events was reported after dose escalation.

CONCLUSION: This study demonstrated that it is feasible to increase the percentage of patients with endoxifen levels ≥ 16 nM using TDM. TDM is a safe strategy that offers the possibility of nearly halving the number of patients with endoxifen levels < 16 nM.

© 2021. The Author(s).

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Publication Types

• Journal Article

Grant support

• Erasmus MC/Erasmus Universiteit Rotterdam
• the Netherlands (grant number 2017-17108/Erasmus Universiteit Rotterdam