Tamoxifen Metabolism and Efficacy in Breast Cancer: A Prospective Multicenter Trial
Patrick Neven, Lynn Jongen, Anneleen Lintermans, Kathleen Van Asten, Chantal Blomme, Diether Lambrechts, An Poppe, Hans Wildiers, Anne-Sophie Dieudonné, Olivier Brouckaert, Jan Decloedt, Patrick Berteloot, Didier Verhoeven, Markus Joerger, Peter Vuylsteke, Wim Wynendaele, Minne Casteels, Sabine Van Huffel, Willem Lybaert, Johan Van Ginderachter, Robert Paridaens, Ignace Vergote, Vincent Olaf Dezentjé, Ben Van Calster & Henk-Jan Guchelaar
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abstract
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Levels of endoxifen, the most active metabolite of tamoxifen, vary
by the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We
prospectively investigated tamoxifen efficacy by serum endoxifen
levels and the tamoxifen activity score (TAS). A prospective
observational multicenter study included postmenopausal women with
an estrogen receptor-positive breast cancer receiving first-line
tamoxifen, 20 mg daily in the neoadjuvant or metastatic setting,
recruited between February 2009 and May 2014. The primary endpoint
was the objective response rate (ORR) using RECIST criteria 1.0.
Secondary endpoints were clinical benefit (CB), progression-free
survival (PFS), and tolerability of tamoxifen. The main analysis
used logistic regression to relate ORR to serum endoxifen levels
after 3 months. Endpoints were also related to other tamoxifen
metabolites and to TAS. Endoxifen levels were available for 247 of
all 297 patients (83%), of which 209 with target lesions (85%).
Median follow-up time for PFS was 32.5 months, and 62% progressed.
ORR and CB were 45% and 84%, respectively. ORR was not related to
endoxifen, and the OR of ORR was 1.008 per μg/L increase in
endoxifen (95% confidence interval, 0.971-1.046; = ). In general,
none of the endpoints was associated with endoxifen levels,
tamoxifen metabolites, or TAS. Under the prespecified assumptions,
the results from this prospective clinical trial do not suggest
therapeutic drug monitoring of endoxifen to be of clinical value in
postmenopausal women treated with tamoxifen for breast cancer in the
neoadjuvant or metastatic setting. .
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citation
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Neven P, Jongen L, Lintermans A, Van Asten K, Blomme C, Lambrechts
D, Poppe A, Wildiers H, Dieudonné A S, Brouckaert O, Decloedt J,
Berteloot P, Verhoeven D, Joerger M, Vuylsteke P, Wynendaele W,
Casteels M, Van Huffel S, Lybaert W, Van Ginderachter J, Paridaens
R, Vergote I, Dezentjé V O, Van Calster B, Guchelaar H J. Tamoxifen
Metabolism and Efficacy in Breast Cancer: A Prospective Multicenter
Trial. Clin Cancer Res 2018; 24:2312-2318.
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type
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journal paper/review (English)
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date of publishing
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19-02-2018
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journal title
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Clin Cancer Res (24/10)
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ISSN print
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1078-0432
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pages
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2312-2318
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PubMed
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29459457
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DOI
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10.1158/1078-0432.CCR-17-3028
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