Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226.

Autor: Rutherford DV; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Medley S; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA., Henderson NC; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA., Gersch CL; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Vandenberg TA; Western University/Canadian Cancer Trials Group, London, ON, N5X 3K8, Canada., Albain KS; Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA., Dakhil SR; Cancer Center of Kansas, Wichita, KS 67214, USA., Tirumali NR; Kaiser Permanente, Beaverton, OR 97005, USA., Gralow JR; American Society of Clinical Oncology, Alexandria, 22314, Virginia., Hortobagyi GN; University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA., Pusztai L; Yale School of Medicine, New Haven, CT 06510, USA., Mehta RS; University of California Irvine Medical Center, Chao Family Comprehensive Cancer Center, Orange, CA 92868, USA., Hayes DF; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Kidwell KM; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA., Henry NL; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Barlow WE; SWOG Statistical Center, Seattle, WA 98109, USA., Rae JM; Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA., Hertz DL; Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.
Jazyk: angličtina
Zdroj: Pharmacogenomics [Pharmacogenomics] 2023 Aug; Vol. 24 (12), pp. 665-673. Date of Electronic Publication: 2023 Aug 24.
DOI: 10.2217/pgs-2023-0097
Abstrakt: Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (β-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.
Databáze: MEDLINE