Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen

P. Fox, B. Balakrishnar, A. Menzies, C. Liddle, S. Coulter, P. Provan, V. Gebski, R. Hui, R. Kefford, N. Wilcken, R. Balleine, H. Gurney

Research output: Contribution to journalMeeting abstractResearchpeer-review

Abstract

Background: The rate-limiting step in tamoxifen biotransformation to
endoxifen is cytochrome p450 2D6 (CYP2D6) activity. CYP2D6 inhibitors
may result in decreased endoxifen levels, although are commonly used to
treat depression and hot fl ushes. The aim of this study was to examine the
association between CYP2D6 inhibitor use and tamoxifen metabolite levels
in breast cancer patients.

Methods: Plasma endoxifen levels were measured using High Performance
Liquid Chromatography/Mass Spectroscopy in 112 patients taking tamoxi-
fen 20 mg daily. Patients co-prescribed CYP2D6 inhibitors were included
in this analysis.

Results: 22 of 112 patients (20%) were co-prescribed tamoxifen and a
CYP2D6 inhibitor. These included 11 minimal, 9 weak-moderate and 2
strong inhibitors. Inhibitors were prescribed for depression/anxiety (n = 11),
hot fl ushes (n = 7) and allergic disorders (n = 4). The mean endoxifen level
in patients taking no inhibitor (n = 90), minimal, weak-moderate and strong
inhibitors were 28.9, 21.3, 23.1 and 4.9 nM, respectively (p = 0.01). There
was an association between the metabolic ratio of endoxifen compared with
its precursor N-desmethyltamoxifen and inhibitor use (p = 0.03), consistent
with an impact of inhibitors on CYP2D6 activity.
Conclusions: CYP2D6 inhibitor use was associated with lower plasma

endoxifen levels in patients taking endoxifen. The interaction between
CYP2D6 inhibitors and other factors that may affect endoxifen levels, in
particular CYP2D6 genotype, is an issue requiring further study.
LanguageEnglish
Pages52-52
Number of pages1
JournalAsia-Pacific Journal of Clinical Oncology
Volume8
Issue numberSupplement 2
Early online date31 Jul 2012
DOIs
Publication statusPublished - 31 Jul 2012
Externally publishedYes

Cite this

Fox, P. ; Balakrishnar, B. ; Menzies, A. ; Liddle, C. ; Coulter, S. ; Provan, P. ; Gebski, V. ; Hui, R. ; Kefford, R. ; Wilcken, N. ; Balleine, R. ; Gurney, H. / Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen. In: Asia-Pacific Journal of Clinical Oncology. 2012 ; Vol. 8, No. Supplement 2. pp. 52-52.
@article{49a751e70a024b979514aced25701182,
title = "Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen",
abstract = "Background: The rate-limiting step in tamoxifen biotransformation to endoxifen is cytochrome p450 2D6 (CYP2D6) activity. CYP2D6 inhibitors may result in decreased endoxifen levels, although are commonly used to treat depression and hot fl ushes. The aim of this study was to examine the association between CYP2D6 inhibitor use and tamoxifen metabolite levels in breast cancer patients.Methods: Plasma endoxifen levels were measured using High Performance Liquid Chromatography/Mass Spectroscopy in 112 patients taking tamoxi-fen 20 mg daily. Patients co-prescribed CYP2D6 inhibitors were included in this analysis.Results: 22 of 112 patients (20{\%}) were co-prescribed tamoxifen and a CYP2D6 inhibitor. These included 11 minimal, 9 weak-moderate and 2 strong inhibitors. Inhibitors were prescribed for depression/anxiety (n = 11), hot fl ushes (n = 7) and allergic disorders (n = 4). The mean endoxifen level in patients taking no inhibitor (n = 90), minimal, weak-moderate and strong inhibitors were 28.9, 21.3, 23.1 and 4.9 nM, respectively (p = 0.01). There was an association between the metabolic ratio of endoxifen compared with its precursor N-desmethyltamoxifen and inhibitor use (p = 0.03), consistent with an impact of inhibitors on CYP2D6 activity.Conclusions: CYP2D6 inhibitor use was associated with lower plasma endoxifen levels in patients taking endoxifen. The interaction between CYP2D6 inhibitors and other factors that may affect endoxifen levels, in particular CYP2D6 genotype, is an issue requiring further study.",
author = "P. Fox and B. Balakrishnar and A. Menzies and C. Liddle and S. Coulter and P. Provan and V. Gebski and R. Hui and R. Kefford and N. Wilcken and R. Balleine and H. Gurney",
year = "2012",
month = "7",
day = "31",
doi = "10.1111/j.1743-7563.2012.01581.x",
language = "English",
volume = "8",
pages = "52--52",
journal = "Asia-Pacific Journal of Clinical Oncology",
issn = "1743-7555",
publisher = "Wiley-Blackwell, Wiley",
number = "Supplement 2",

}

Fox, P, Balakrishnar, B, Menzies, A, Liddle, C, Coulter, S, Provan, P, Gebski, V, Hui, R, Kefford, R, Wilcken, N, Balleine, R & Gurney, H 2012, 'Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen', Asia-Pacific Journal of Clinical Oncology, vol. 8, no. Supplement 2, pp. 52-52. https://doi.org/10.1111/j.1743-7563.2012.01581.x

Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen. / Fox, P.; Balakrishnar, B.; Menzies, A.; Liddle, C.; Coulter, S.; Provan, P.; Gebski, V.; Hui, R.; Kefford, R.; Wilcken, N.; Balleine, R.; Gurney, H.

In: Asia-Pacific Journal of Clinical Oncology, Vol. 8, No. Supplement 2, 31.07.2012, p. 52-52.

Research output: Contribution to journalMeeting abstractResearchpeer-review

TY - JOUR

T1 - Concomitant CYP2D6 inhibitor use and plasma metabolite levels in breast cancer patients treated with tamoxifen

AU - Fox, P.

AU - Balakrishnar, B.

AU - Menzies, A.

AU - Liddle, C.

AU - Coulter, S.

AU - Provan, P.

AU - Gebski, V.

AU - Hui, R.

AU - Kefford, R.

AU - Wilcken, N.

AU - Balleine, R.

AU - Gurney, H.

PY - 2012/7/31

Y1 - 2012/7/31

N2 - Background: The rate-limiting step in tamoxifen biotransformation to endoxifen is cytochrome p450 2D6 (CYP2D6) activity. CYP2D6 inhibitors may result in decreased endoxifen levels, although are commonly used to treat depression and hot fl ushes. The aim of this study was to examine the association between CYP2D6 inhibitor use and tamoxifen metabolite levels in breast cancer patients.Methods: Plasma endoxifen levels were measured using High Performance Liquid Chromatography/Mass Spectroscopy in 112 patients taking tamoxi-fen 20 mg daily. Patients co-prescribed CYP2D6 inhibitors were included in this analysis.Results: 22 of 112 patients (20%) were co-prescribed tamoxifen and a CYP2D6 inhibitor. These included 11 minimal, 9 weak-moderate and 2 strong inhibitors. Inhibitors were prescribed for depression/anxiety (n = 11), hot fl ushes (n = 7) and allergic disorders (n = 4). The mean endoxifen level in patients taking no inhibitor (n = 90), minimal, weak-moderate and strong inhibitors were 28.9, 21.3, 23.1 and 4.9 nM, respectively (p = 0.01). There was an association between the metabolic ratio of endoxifen compared with its precursor N-desmethyltamoxifen and inhibitor use (p = 0.03), consistent with an impact of inhibitors on CYP2D6 activity.Conclusions: CYP2D6 inhibitor use was associated with lower plasma endoxifen levels in patients taking endoxifen. The interaction between CYP2D6 inhibitors and other factors that may affect endoxifen levels, in particular CYP2D6 genotype, is an issue requiring further study.

AB - Background: The rate-limiting step in tamoxifen biotransformation to endoxifen is cytochrome p450 2D6 (CYP2D6) activity. CYP2D6 inhibitors may result in decreased endoxifen levels, although are commonly used to treat depression and hot fl ushes. The aim of this study was to examine the association between CYP2D6 inhibitor use and tamoxifen metabolite levels in breast cancer patients.Methods: Plasma endoxifen levels were measured using High Performance Liquid Chromatography/Mass Spectroscopy in 112 patients taking tamoxi-fen 20 mg daily. Patients co-prescribed CYP2D6 inhibitors were included in this analysis.Results: 22 of 112 patients (20%) were co-prescribed tamoxifen and a CYP2D6 inhibitor. These included 11 minimal, 9 weak-moderate and 2 strong inhibitors. Inhibitors were prescribed for depression/anxiety (n = 11), hot fl ushes (n = 7) and allergic disorders (n = 4). The mean endoxifen level in patients taking no inhibitor (n = 90), minimal, weak-moderate and strong inhibitors were 28.9, 21.3, 23.1 and 4.9 nM, respectively (p = 0.01). There was an association between the metabolic ratio of endoxifen compared with its precursor N-desmethyltamoxifen and inhibitor use (p = 0.03), consistent with an impact of inhibitors on CYP2D6 activity.Conclusions: CYP2D6 inhibitor use was associated with lower plasma endoxifen levels in patients taking endoxifen. The interaction between CYP2D6 inhibitors and other factors that may affect endoxifen levels, in particular CYP2D6 genotype, is an issue requiring further study.

U2 - 10.1111/j.1743-7563.2012.01581.x

DO - 10.1111/j.1743-7563.2012.01581.x

M3 - Meeting abstract

VL - 8

SP - 52

EP - 52

JO - Asia-Pacific Journal of Clinical Oncology

T2 - Asia-Pacific Journal of Clinical Oncology

JF - Asia-Pacific Journal of Clinical Oncology

SN - 1743-7555

IS - Supplement 2

ER -