guest ::
| Home > Publications database > Supplementation of Tamoxifen with Low-Dose Endoxifen in Patients with Breast Cancer with Impaired Tamoxifen Metabolism (TAMENDOX): A Randomized Controlled Phase I/II Trial. |
| Home > Publications database > Supplementation of Tamoxifen with Low-Dose Endoxifen in Patients with Breast Cancer with Impaired Tamoxifen Metabolism (TAMENDOX): A Randomized Controlled Phase I/II Trial. |
| Journal Article | DKFZ-2025-02672 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2025
AACR
Philadelphia, Pa. [u.a.]
Abstract: :Tamoxifen undergoes bioactivation to its active metabolite (Z)-endoxifen, which blocks estrogen-dependent breast tumor growth at high potency. We tested the feasibility and safety of supplementing standard tamoxifen therapy with low-dose (Z)-endoxifen in patients with breast cancer with compromised tamoxifen bioactivation.:We conducted a prospective, interventional, three group randomized trial including 235 patients with hormone receptor-positive breast cancer who received standard tamoxifen therapy (20 mg/day). Patients were stratified by CYP2D6 genotype (n = 78), defining poor, intermediate, and normal metabolizers, or by baseline (Z)-endoxifen plasma concentration (n = 78), defining ≤15, 15 to 25, and ≥25 nmol/L. Co-treatment with (Z)-endoxifen 3 and 1.5 mg/day or placebo was performed, respectively. A control group (n = 79) received placebo regardless of metabolizer phenotype. The primary endpoint was the number of patients with (Z)-endoxifen levels >32 nmol/L after 6 weeks of treatment. Adverse events were continuously monitored.A higher proportion of patients in both intervention groups achieved target concentrations >32 nmol/L compared with control (P < 0.0001). At 3 mg (Z)-endoxifen supplementation, 92.3% of CYP2D6 poor metabolizer patients and all patients with baseline (Z)-endoxifen ≤15 nmol/L achieved the target concentration. At 1.5 mg (Z)-endoxifen supplementation, 88% of CYP2D6 intermediate metabolizer patients and 95% of patients with 15 to 25 nmol/L baseline (Z)-endoxifen levels achieved the target concentration. Similar proportions of patients receiving (Z)-endoxifen (6/80, 7.5%) or placebo (8/155, 5.2%) experienced grade 3 adverse events.Adding low-dose (Z)-endoxifen to standard tamoxifen is safe and provides a new approach to personalized antiestrogen treatment for patients with low endoxifen plasma levels.
Keyword(s): Humans (MeSH) ; Female (MeSH) ; Breast Neoplasms: drug therapy (MeSH) ; Breast Neoplasms: pathology (MeSH) ; Breast Neoplasms: genetics (MeSH) ; Breast Neoplasms: metabolism (MeSH) ; Tamoxifen: administration & dosage (MeSH) ; Tamoxifen: analogs & derivatives (MeSH) ; Tamoxifen: pharmacokinetics (MeSH) ; Tamoxifen: adverse effects (MeSH) ; Middle Aged (MeSH) ; Cytochrome P-450 CYP2D6: genetics (MeSH) ; Aged (MeSH) ; Adult (MeSH) ; Antineoplastic Agents, Hormonal: administration & dosage (MeSH) ; Antineoplastic Agents, Hormonal: adverse effects (MeSH) ; Prospective Studies (MeSH) ; Treatment Outcome (MeSH) ; Aged, 80 and over (MeSH) ; Genotype (MeSH) ; Tamoxifen ; Cytochrome P-450 CYP2D6 ; 4-hydroxy-N-desmethyltamoxifen ; Antineoplastic Agents, Hormonal
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
