Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
24
02
2023
accepted:
20
04
2023
revised:
19
04
2023
medline:
30
6
2023
pubmed:
7
5
2023
entrez:
6
5
2023
Statut:
ppublish
Résumé
Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women. In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status. Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women. Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings. ClinicalTrials.gov ID: NCT03346200.
Sections du résumé
BACKGROUND
Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women.
METHODS
In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status.
RESULTS
Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women.
CONCLUSIONS
Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings.
TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT03346200.
Identifiants
pubmed: 37149701
doi: 10.1038/s41416-023-02293-z
pii: 10.1038/s41416-023-02293-z
pmc: PMC10307785
doi:
Substances chimiques
Tamoxifen
094ZI81Y45
Antineoplastic Agents, Hormonal
0
Banques de données
ClinicalTrials.gov
['NCT03346200']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
61-71Informations de copyright
© 2023. The Author(s).
Références
JAMA. 2006 Jun 21;295(23):2742-51
pubmed: 16754728
JAMA. 2006 Jun 21;295(23):2727-41
pubmed: 16754727
Eur J Cancer. 1994;30A(9):1326-36
pubmed: 7999421
J Pain Symptom Manage. 2013 Jul;46(1):131-41
pubmed: 23195392
Breast Cancer Res Treat. 2012 Jul;134(2):875-80
pubmed: 22622807
Cancer Prev Res (Phila). 2011 Sep;4(9):1360-5
pubmed: 21893499
Lancet. 2013 Mar 9;381(9869):805-16
pubmed: 23219286
J Clin Oncol. 2010 Jun 20;28(18):3090-5
pubmed: 20458026
Breast Cancer Res Treat. 2008 Jan;107(2):167-80
pubmed: 17876703
Br J Cancer. 2008 Dec 2;99(11):1763-8
pubmed: 18985046
JAMA. 2019 Sep 3;322(9):857-867
pubmed: 31479144
J Clin Oncol. 2015 Jul 10;33(20):2262-9
pubmed: 26033800
J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88
pubmed: 9747868
JAMA. 2019 Sep 3;322(9):868-886
pubmed: 31479143
J Clin Oncol. 1999 Sep;17(9):2659-69
pubmed: 10561339
PLoS One. 2013 Dec 04;8(12):e81653
pubmed: 24324712
J Allergy Clin Immunol. 2003 Nov;112(5 Suppl):S107-11
pubmed: 14586395
Lancet. 2002 Sep 14;360(9336):817-24
pubmed: 12243915
Lancet Oncol. 2002 Apr;3(4):207-14
pubmed: 12067682
Breast Cancer Res Treat. 2006 Sep;99(2):215-20
pubmed: 16541307
Breast Cancer Res. 2020 Aug 26;22(1):95
pubmed: 32847607
Lancet. 1998 Jul 11;352(9122):98-101
pubmed: 9672274
N Engl J Med. 2001 Jun 28;344(26):1997-2008
pubmed: 11430330
Breast Cancer Res Treat. 2018 Aug;170(3):487-497
pubmed: 29603032
Breast Cancer Res Treat. 1999 May;55(2):189-99
pubmed: 10481946
Clin Cancer Res. 2021 Feb 15;27(4):967-974
pubmed: 33272980
Ann Oncol. 2016 Apr;27(4):575-90
pubmed: 26646754
Breast Cancer Res Treat. 2012 Oct;135(3):663-80
pubmed: 22903689
Lancet. 1998 May 16;351(9114):1451-67
pubmed: 9605801
Cancer. 2006 Feb 1;106(3):505-13
pubmed: 16369994
J Clin Oncol. 2001 Apr 1;19(7):1885-92
pubmed: 11283119
Breast Cancer Res Treat. 2014 Nov;148(1):1-5
pubmed: 25292419
Breast. 2021 Aug;58:147-159
pubmed: 34049260
J Natl Cancer Inst. 2015 Nov 27;108(4):
pubmed: 26615179
Cancer Treat Rev. 2021 Nov;100:102264
pubmed: 34388473
J Clin Oncol. 2021 Jun 10;39(17):1899-1908
pubmed: 33734864
J Clin Oncol. 2019 Jul 1;37(19):1629-1637
pubmed: 30973790
J Clin Oncol. 2023 Jun 10;41(17):3116-3121
pubmed: 36917758
Ann N Y Acad Sci. 2001 Dec;949:143-50
pubmed: 11795346
J Clin Oncol. 2017 Aug 10;35(23):2666-2673
pubmed: 28661758
Lancet. 2011 Aug 27;378(9793):771-84
pubmed: 21802721
Int J Cancer. 2023 Jun 1;152(11):2362-2372
pubmed: 36637153
NPJ Breast Cancer. 2017 May 19;3:20
pubmed: 28649660