%0 Journal Article
%A Mürdter, Thomas E
%A Schroth, Werner
%A Goetz, Matthew P
%A Tremmel, Roman
%A Igel, Svitlana
%A Schaeffeler, Elke
%A Jäger, Simon
%A Loibl, Sibylle
%A Gerteis, Andreas
%A Pfaff, Lena
%A Bechtner, Christina
%A Wrobel, Denise
%A Bernhöft, Ilka
%A Fischer, Imma
%A Meisner, Christoph
%A Block, Michael
%A Brauch, Hiltrud
%A Schwab, Matthias
%T Supplementation of Tamoxifen with Low-Dose Endoxifen in Patients with Breast Cancer with Impaired Tamoxifen Metabolism (TAMENDOX): A Randomized Controlled Phase I/II Trial.
%J Clinical cancer research
%V 31
%N 23
%@ 1078-0432
%C Philadelphia, Pa. [u.a.]
%I AACR
%M DKFZ-2025-02672
%P 4903 - 4911
%D 2025
%X :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
%K Humans
%K Female
%K Breast Neoplasms: drug therapy
%K Breast Neoplasms: pathology
%K Breast Neoplasms: genetics
%K Breast Neoplasms: metabolism
%K Tamoxifen: administration & dosage
%K Tamoxifen: analogs & derivatives
%K Tamoxifen: pharmacokinetics
%K Tamoxifen: adverse effects
%K Middle Aged
%K Cytochrome P-450 CYP2D6: genetics
%K Aged
%K Adult
%K Antineoplastic Agents, Hormonal: administration & dosage
%K Antineoplastic Agents, Hormonal: adverse effects
%K Prospective Studies
%K Treatment Outcome
%K Aged, 80 and over
%K Genotype
%K Tamoxifen (NLM Chemicals)
%K Cytochrome P-450 CYP2D6 (NLM Chemicals)
%K 4-hydroxy-N-desmethyltamoxifen (NLM Chemicals)
%K Antineoplastic Agents, Hormonal (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41036998
%R 10.1158/1078-0432.CCR-25-2103
%U https://inrepo02.dkfz.de/record/306679