TY  - JOUR
AU  - Mürdter, Thomas E
AU  - Schroth, Werner
AU  - Goetz, Matthew P
AU  - Tremmel, Roman
AU  - Igel, Svitlana
AU  - Schaeffeler, Elke
AU  - Jäger, Simon
AU  - Loibl, Sibylle
AU  - Gerteis, Andreas
AU  - Pfaff, Lena
AU  - Bechtner, Christina
AU  - Wrobel, Denise
AU  - Bernhöft, Ilka
AU  - Fischer, Imma
AU  - Meisner, Christoph
AU  - Block, Michael
AU  - Brauch, Hiltrud
AU  - Schwab, Matthias
TI  - Supplementation of Tamoxifen with Low-Dose Endoxifen in Patients with Breast Cancer with Impaired Tamoxifen Metabolism (TAMENDOX): A Randomized Controlled Phase I/II Trial.
JO  - Clinical cancer research
VL  - 31
IS  - 23
SN  - 1078-0432
CY  - Philadelphia, Pa. [u.a.]
PB  - AACR
M1  - DKFZ-2025-02672
SP  - 4903 - 4911
PY  - 2025
AB  - :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
KW  - Humans
KW  - Female
KW  - Breast Neoplasms: drug therapy
KW  - Breast Neoplasms: pathology
KW  - Breast Neoplasms: genetics
KW  - Breast Neoplasms: metabolism
KW  - Tamoxifen: administration & dosage
KW  - Tamoxifen: analogs & derivatives
KW  - Tamoxifen: pharmacokinetics
KW  - Tamoxifen: adverse effects
KW  - Middle Aged
KW  - Cytochrome P-450 CYP2D6: genetics
KW  - Aged
KW  - Adult
KW  - Antineoplastic Agents, Hormonal: administration & dosage
KW  - Antineoplastic Agents, Hormonal: adverse effects
KW  - Prospective Studies
KW  - Treatment Outcome
KW  - Aged, 80 and over
KW  - Genotype
KW  - Tamoxifen (NLM Chemicals)
KW  - Cytochrome P-450 CYP2D6 (NLM Chemicals)
KW  - 4-hydroxy-N-desmethyltamoxifen (NLM Chemicals)
KW  - Antineoplastic Agents, Hormonal (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41036998
DO  - DOI:10.1158/1078-0432.CCR-25-2103
UR  - https://inrepo02.dkfz.de/record/306679
ER  -