The Influences of Adherence to Tamoxifen and CYP2D6 Pharmacogenetics on Plasma Concentrations of the Active Metabolite (Z)-Endoxifen in Breast Cancer.

Autor: Nardin JM; Clinical Research Department, Erasto Gaertner Hospital, Curitiba, Brazil.; School of Health Science, UniBrasil, Curitiba, Brazil.; Pontifical Catholic University of Parana, Curitiba, Brazil., Schroth W; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tuebingen, Tuebingen, Germany., Almeida TA; Clinical Oncology Department, Erasto Gaertner Hospital, Curitiba, Brazil., Mürdter T; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tuebingen, Tuebingen, Germany., Picolotto S; Pharmacy Department, Erasto Gaertner Hospital, Curitiba, Brazil., Vendramini ECL; Pharmacy Department, Erasto Gaertner Hospital, Curitiba, Brazil., Hoppe R; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tuebingen, Tuebingen, Germany., Kogin JP; School of Health Science, UniBrasil, Curitiba, Brazil., Miqueleto D; School of Health Science, UniBrasil, Curitiba, Brazil., de Moraes SDR; School of Health Science, UniBrasil, Curitiba, Brazil., Schwab M; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; Departments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; iFIT Cluster of Excellence, University of Tuebingen, Tuebingen, Germany., Pecoits-Filho RF; Pontifical Catholic University of Parana, Curitiba, Brazil., Brauch H; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tuebingen, Tuebingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; iFIT Cluster of Excellence, University of Tuebingen, Tuebingen, Germany., Casali-da-Rocha JC; Pontifical Catholic University of Parana, Curitiba, Brazil.; Department of Oncogenetics, Erasto Gaertner Hospital, Curitiba, Brazil.
Jazyk: angličtina
Zdroj: Clinical and translational science [Clin Transl Sci] 2020 Mar; Vol. 13 (2), pp. 284-292. Date of Electronic Publication: 2019 Nov 09.
DOI: 10.1111/cts.12707
Abstrakt: Tamoxifen efficacy in breast cancer is suspected to depend on adherence and intact drug metabolism. We evaluated the role of adherence behavior and pharmacogenetics on the formation rate of (Z)-endoxifen. In 192 Brazilian patients, we assessed plasma levels of tamoxifen and its metabolites at 3, 6, and 12 months of treatment (liquid-chromatography tandem mass spectrometry), adherence behavior (Morisky, Green, and Levine medication adherence scale), and cytochrome P450 2D6 (CYP2D6) and other pharmacogene polymorphisms (matrix-assisted laser-desorption-ionization time of flight) mass spectrometry, real-time polymerase chain reaction). Adherence explained 47% of the variability of tamoxifen plasma concentrations (P < 0.001). Although CYP2D6 alone explained 26.4%, the combination with adherence explained 40% of (Z)-endoxifen variability at 12 months (P < 0.001). The influence of low adherence to not achieving relevant (Z)-endoxifen levels was highest in patients with noncompromised CYP2D6 function (relative risk 3.65; 95% confidence interval 1.48-8.99). As a proof-of-concept, we demonstrated that (Z)-endoxifen levels are influenced both by patient adherence to tamoxifen and CYP2D6, which is particularly relevant for patients with full CYP2D6 function.
(© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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