Clara I Lee1, Peter Fox2, Bavanthi Balakrishnar2, Rosemary L Balleine3, Bo Gao2, Pamela Provan4, Sally Coulter5, Christopher Liddle5, Rina Hui4, Mark Wong4, Howard Gurney6, Nicholas Wilcken4. 1. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Department of Medical Oncology, Bankstown-Lidcombe Hospital, Bankstown, Australia; Faculty of Medicine, University of New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia. Electronic address: clara.lee@health.nsw.gov.au. 2. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia. 3. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Westmead Institute for Medical Research, Westmead, Australia. 4. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia. 5. Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia; Westmead Institute for Medical Research, Westmead, Australia. 6. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, Australia; Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia; Macquarie University, Australia.
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.
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 tamoxifentoxicities. 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.
Authors: Clara Inkyung Lee; Siew Kee Low; Ricardo Maldonado; Peter Fox; Bavanthi Balakrishnar; Sally Coulter; Peter de Bruijn; Stijn L W Koolen; Bo Gao; Jodi Lynch; Nicholas Zdenkowski; Rina Hui; Christopher Liddle; Ron H J Mathijssen; Nicholas Wilcken; Mark Wong; Howard Gurney Journal: Breast Date: 2020-10-21 Impact factor: 4.380
Authors: Chiara Jeiziner; Céline K Stäuble; Markus L Lampert; Kurt E Hersberger; Henriette E Meyer Zu Schwabedissen Journal: Pharmgenomics Pers Med Date: 2021-02-19
Authors: Carmen W H Chan; Bernard M H Law; Marques S N Ng; Corinna C Y Wong; Carissa W Y Wong; Morgan Quinley; Jessica M Orgusyan; Ka Ming Chow; Mary M Y Waye Journal: BMC Cancer Date: 2021-05-18 Impact factor: 4.430