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Evaluation of the effects of increasing tamoxifen dose based on CYP2D6 genotype on the concentration tamoxifen and its metabolites in breast cancer patients

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Year: 2018
COI code: IPMCMED03_087
Paper Language: English

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Authors Evaluation of the effects of increasing tamoxifen dose based on CYP2D6 genotype on the concentration tamoxifen and its metabolites in breast cancer patients

  Zahra Khalaj - Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  Zohreh Baratieh - Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  Parvaneh Nikpour - Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran- 3Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan Univ
Matthias Schwab - Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany- Department of Clinical Pharmacology, University Hospital Tubingen, Tubingen, Germany- Department of Pharmacy and Biochemistry, University Hospital Tubingen, Tubingen, Germ

Abstract:

Introduction: The polymorphic enzyme cytochrome P450 2D6 (CYP2D6) catalyses a major step in the bioactivation of tamoxifen. Genotyping of clinically relevant CYP2D6 alleles and subsequent dose adjustment is a promising approach to individualize breast cancer therapy. The aim of this study was to investigate the relationship between the plasma levels of tamoxifen and its metabolites and different CYP2D6 genotypes under standard (20 mg/d) and dose-adjusted therapy (Registration ID in Iranian Registry of Clinical Trials: IRCT2015082323734N1).Material and methods: Using TaqMan® assays common alleles of CYP2D6 (*1, *2, *4, *5, *6, *10, *17 and *41) were identified in 134 breast cancer patients. Based on CYP2D6 genotypes patients with an activity score 1 (n=15) and 0 to 0.5 (n=2) were treated with tamoxifen adjusted dosage of 30 and 40 mg/d, respectively. The concentration of tamoxifen and its metabolites before and after 4 and 8 months of dose adjustment were measured using LC-MS/MS technology.Results: At baseline, (Z)-endoxifen plasma concentrations and the metabolic ratio (Z)-Endoxifen / N-desmethyltamoxifen correlated with CYP2D6 genotype (Kruskal-Wallis p=0.013 and p<0.0001, respectively). Dose escalation to 30 and 40 mg/d in patients with a CYP2D6 activity score of 1 (n=15) and 0-0.5 (n=2) resulted in a significant increase in (Z)-endoxifen plasma levels (Friedman p= 0.0388) along with the plasma concentrations of tamoxifen and its other metabolites. Conclusions: For the first time, we show the feasibility of dose escalation of tamoxifen in breast cancer patients with compromised CYP2D6 activity and Iranian ethnic background to increase the plasma concentrations of (Z)-endoxifen.

Keywords:

CYP2D6, dose, endoxifen, genotype, metabolite, tamoxifen

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COI code: IPMCMED03_087

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Khalaj, Zahra; Zohreh Baratieh; Parvaneh Nikpour & Matthias Schwab, 2018, Evaluation of the effects of increasing tamoxifen dose based on CYP2D6 genotype on the concentration tamoxifen and its metabolites in breast cancer patients, Third International Private Medical Congress of Iran, تهران, دانشگاه علوم پزشكي بقيه الله(عج), https://www.civilica.com/Paper-IPMCMED03-IPMCMED03_087.htmlInside the text, wherever referred to or an achievement of this article is mentioned, after mentioning the article, inside the parental, the following specifications are written.
First Time: (Khalaj, Zahra; Zohreh Baratieh; Parvaneh Nikpour & Matthias Schwab, 2018)
Second and more: (Khalaj; Baratieh; Nikpour & Schwab, 2018)
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Type: Medical University
Paper No.: 3184
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