Uridine Glucuronosyltransferase 2B7 Polymorphism-Based Pharmacogenetic Dosing of Epirubicin in FEC Chemotherapy for Early-Stage Breast Cancer.


Journal

Clinical breast cancer
ISSN: 1938-0666
Titre abrégé: Clin Breast Cancer
Pays: United States
ID NLM: 100898731

Informations de publication

Date de publication:
10 2021
Historique:
received: 13 10 2020
revised: 22 02 2021
accepted: 01 03 2021
pubmed: 10 4 2021
medline: 5 2 2022
entrez: 9 4 2021
Statut: ppublish

Résumé

Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7). Patients homozygous for the minor allele (CC) in the UGT2B7 -161 promoter polymorphism have lower clearance and significantly higher rates of leukopenia compared to wild-type homozygote (TT) or heterozygote (CT) patients. This study was designed to determine if TT and CT genotype patients could tolerate a higher epirubicin dose compared to CC genotype patients. We studied women with histologically confirmed non-metastatic, invasive breast cancer who were scheduled to receive at least three cycles of FE Forty-five patients were enrolled (10 CC, 21 CT, and 14 TT genotypes) and received 100 mg/m Pharmacogenetically guided epirubicin dosing is well tolerated and allowed dose escalation without increased toxicity.

Sections du résumé

BACKGROUND
Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7). Patients homozygous for the minor allele (CC) in the UGT2B7 -161 promoter polymorphism have lower clearance and significantly higher rates of leukopenia compared to wild-type homozygote (TT) or heterozygote (CT) patients. This study was designed to determine if TT and CT genotype patients could tolerate a higher epirubicin dose compared to CC genotype patients.
PATIENTS AND METHODS
We studied women with histologically confirmed non-metastatic, invasive breast cancer who were scheduled to receive at least three cycles of FE
RESULTS
Forty-five patients were enrolled (10 CC, 21 CT, and 14 TT genotypes) and received 100 mg/m
CONCLUSION
Pharmacogenetically guided epirubicin dosing is well tolerated and allowed dose escalation without increased toxicity.

Identifiants

pubmed: 33832852
pii: S1526-8209(21)00056-2
doi: 10.1016/j.clbc.2021.03.001
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Epirubicin 3Z8479ZZ5X
Cyclophosphamide 8N3DW7272P
UGT2B7 protein, human EC 2.4.1.-
Glucuronosyltransferase EC 2.4.1.17

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e584-e593

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Auteurs

Anil A Joy (AA)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Larissa J Vos (LJ)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada.

Edith Pituskin (E)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Faculty of Nursing, University of Alberta, Edmonton, AB, Canada.

Sarah F Cook (SF)

Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY.

Robert R Bies (RR)

Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY.

Ann Vlahadamis (A)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada.

Karen King (K)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Sanraj K Basi (SK)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Judith Meza-Junco (J)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

John R Mackey (JR)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Avalyn Stanislaus (A)

Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Vijaya L Damaraju (VL)

Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Sambasivarao Damaraju (S)

Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Michael B Sawyer (MB)

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada; Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. Electronic address: sawyer@ahs.ca.

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