Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy?

Clara I. Lee, Peter Fox, Bavanthi Balakrishnar, Rosemary L. Balleine, Bo Gao, Pamela Provan, Sally Coulter, Christopher Liddle, Rina Hui, Mark Wong, Howard Gurney, Nicholas Wilcken

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: Severe hot flash (HF)toxicity due to tamoxifen can compromise compliance. We previously found that HFs did not correlate with endoxifen level or CYP2D6 genotype. In this study, we reduced tamoxifen dose in patients with severe HFs to determine whether HFs were ameliorated whilst maintaining a purported therapeutic endoxifen level of >15 nM. Materials and methods: Twenty patients with severe HFs on 20 mg TAM had CYP2D6genotype, trough level tamoxifen and metabolites measured with Loprinzi HF scores (HFS)derived before and after DR of tamoxifen to 10 mg. Other data collected included demographics, smoking, alcohol, menstrual and breast cancer history, previous chemotherapies, concurrent medications, BMI and other tamoxifen toxicities. Results: At the 20 mg tamoxifen dose, endoxifen levels were 25.6, 0–91.9 nM (median, range)with HFS 131, 22–1482 (median, range). Upon DR to 10 mg, median endoxifen level fell to 14.1, 0.6–71.9 nM (difference in means p = 0.11, two-tailed T test)with HFS 47, 5–864 (difference in means p = 0.24, two-tailed T test). Despite lacking statistical significance, 85% of patients reported subjective improvement of HFs with DR. After DR, the proportion of patients with endoxifen level <15 nM increased from 20% to 50%. HFS did not correlate with any other parameter. Conclusion: DR of tamoxifen from 20 mg to 10 mg daily resulted in halving of endoxifen levels and subjective improvement of HF. While half the dose-reduced patients were below a potential therapeutic level of endoxifen, other recent studies suggest that low endoxifen levels may not indicate reduced effectiveness of tamoxifen.

LanguageEnglish
Pages52-57
Number of pages6
JournalBreast
Volume46
DOIs
Publication statusPublished - 1 Aug 2019

Fingerprint

Hot Flashes
Tamoxifen
Cytochrome P-450 CYP2D6
4-hydroxy-N-desmethyltamoxifen
Compliance
Smoking
Genotype
Alcohols
Demography
Breast Neoplasms
Drug Therapy

Keywords

  • Dose reduction
  • Endoxifen
  • Hot flashes
  • Tamoxifen

Cite this

Lee, C. I., Fox, P., Balakrishnar, B., Balleine, R. L., Gao, B., Provan, P., ... Wilcken, N. (2019). Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy? Breast, 46, 52-57. https://doi.org/10.1016/j.breast.2019.05.009
Lee, Clara I. ; Fox, Peter ; Balakrishnar, Bavanthi ; Balleine, Rosemary L. ; Gao, Bo ; Provan, Pamela ; Coulter, Sally ; Liddle, Christopher ; Hui, Rina ; Wong, Mark ; Gurney, Howard ; Wilcken, Nicholas. / Tamoxifen-induced severe hot flashes and endoxifen levels : is dose reduction a safe and effective strategy?. In: Breast. 2019 ; Vol. 46. pp. 52-57.
@article{c4585aec9d154e54885e0638c7488f1b,
title = "Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy?",
abstract = "Objectives: Severe hot flash (HF)toxicity due to tamoxifen can compromise compliance. We previously found that HFs did not correlate with endoxifen level or CYP2D6 genotype. In this study, we reduced tamoxifen dose in patients with severe HFs to determine whether HFs were ameliorated whilst maintaining a purported therapeutic endoxifen level of >15 nM. Materials and methods: Twenty patients with severe HFs on 20 mg TAM had CYP2D6genotype, trough level tamoxifen and metabolites measured with Loprinzi HF scores (HFS)derived before and after DR of tamoxifen to 10 mg. Other data collected included demographics, smoking, alcohol, menstrual and breast cancer history, previous chemotherapies, concurrent medications, BMI and other tamoxifen toxicities. Results: At the 20 mg tamoxifen dose, endoxifen levels were 25.6, 0–91.9 nM (median, range)with HFS 131, 22–1482 (median, range). Upon DR to 10 mg, median endoxifen level fell to 14.1, 0.6–71.9 nM (difference in means p = 0.11, two-tailed T test)with HFS 47, 5–864 (difference in means p = 0.24, two-tailed T test). Despite lacking statistical significance, 85{\%} of patients reported subjective improvement of HFs with DR. After DR, the proportion of patients with endoxifen level <15 nM increased from 20{\%} to 50{\%}. HFS did not correlate with any other parameter. Conclusion: DR of tamoxifen from 20 mg to 10 mg daily resulted in halving of endoxifen levels and subjective improvement of HF. While half the dose-reduced patients were below a potential therapeutic level of endoxifen, other recent studies suggest that low endoxifen levels may not indicate reduced effectiveness of tamoxifen.",
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Lee, CI, Fox, P, Balakrishnar, B, Balleine, RL, Gao, B, Provan, P, Coulter, S, Liddle, C, Hui, R, Wong, M, Gurney, H & Wilcken, N 2019, 'Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy?', Breast, vol. 46, pp. 52-57. https://doi.org/10.1016/j.breast.2019.05.009

Tamoxifen-induced severe hot flashes and endoxifen levels : is dose reduction a safe and effective strategy? / Lee, Clara I.; Fox, Peter; Balakrishnar, Bavanthi; Balleine, Rosemary L.; Gao, Bo; Provan, Pamela; Coulter, Sally; Liddle, Christopher; Hui, Rina; Wong, Mark; Gurney, Howard; Wilcken, Nicholas.

In: Breast, Vol. 46, 01.08.2019, p. 52-57.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Tamoxifen-induced severe hot flashes and endoxifen levels

T2 - Breast

AU - Lee, Clara I.

AU - Fox, Peter

AU - Balakrishnar, Bavanthi

AU - Balleine, Rosemary L.

AU - Gao, Bo

AU - Provan, Pamela

AU - Coulter, Sally

AU - Liddle, Christopher

AU - Hui, Rina

AU - Wong, Mark

AU - Gurney, Howard

AU - Wilcken, Nicholas

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Objectives: Severe hot flash (HF)toxicity due to tamoxifen can compromise compliance. We previously found that HFs did not correlate with endoxifen level or CYP2D6 genotype. In this study, we reduced tamoxifen dose in patients with severe HFs to determine whether HFs were ameliorated whilst maintaining a purported therapeutic endoxifen level of >15 nM. Materials and methods: Twenty patients with severe HFs on 20 mg TAM had CYP2D6genotype, trough level tamoxifen and metabolites measured with Loprinzi HF scores (HFS)derived before and after DR of tamoxifen to 10 mg. Other data collected included demographics, smoking, alcohol, menstrual and breast cancer history, previous chemotherapies, concurrent medications, BMI and other tamoxifen toxicities. Results: At the 20 mg tamoxifen dose, endoxifen levels were 25.6, 0–91.9 nM (median, range)with HFS 131, 22–1482 (median, range). Upon DR to 10 mg, median endoxifen level fell to 14.1, 0.6–71.9 nM (difference in means p = 0.11, two-tailed T test)with HFS 47, 5–864 (difference in means p = 0.24, two-tailed T test). Despite lacking statistical significance, 85% of patients reported subjective improvement of HFs with DR. After DR, the proportion of patients with endoxifen level <15 nM increased from 20% to 50%. HFS did not correlate with any other parameter. Conclusion: DR of tamoxifen from 20 mg to 10 mg daily resulted in halving of endoxifen levels and subjective improvement of HF. While half the dose-reduced patients were below a potential therapeutic level of endoxifen, other recent studies suggest that low endoxifen levels may not indicate reduced effectiveness of tamoxifen.

AB - Objectives: Severe hot flash (HF)toxicity due to tamoxifen can compromise compliance. We previously found that HFs did not correlate with endoxifen level or CYP2D6 genotype. In this study, we reduced tamoxifen dose in patients with severe HFs to determine whether HFs were ameliorated whilst maintaining a purported therapeutic endoxifen level of >15 nM. Materials and methods: Twenty patients with severe HFs on 20 mg TAM had CYP2D6genotype, trough level tamoxifen and metabolites measured with Loprinzi HF scores (HFS)derived before and after DR of tamoxifen to 10 mg. Other data collected included demographics, smoking, alcohol, menstrual and breast cancer history, previous chemotherapies, concurrent medications, BMI and other tamoxifen toxicities. Results: At the 20 mg tamoxifen dose, endoxifen levels were 25.6, 0–91.9 nM (median, range)with HFS 131, 22–1482 (median, range). Upon DR to 10 mg, median endoxifen level fell to 14.1, 0.6–71.9 nM (difference in means p = 0.11, two-tailed T test)with HFS 47, 5–864 (difference in means p = 0.24, two-tailed T test). Despite lacking statistical significance, 85% of patients reported subjective improvement of HFs with DR. After DR, the proportion of patients with endoxifen level <15 nM increased from 20% to 50%. HFS did not correlate with any other parameter. Conclusion: DR of tamoxifen from 20 mg to 10 mg daily resulted in halving of endoxifen levels and subjective improvement of HF. While half the dose-reduced patients were below a potential therapeutic level of endoxifen, other recent studies suggest that low endoxifen levels may not indicate reduced effectiveness of tamoxifen.

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