Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care

A sensitive and selective HPLC–MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N -desmethyltamoxifen ( E )-endoxifen, ( Z )-endoxifen, N -desmethyl-4′-hydroxytamoxifen, 4-hydroxytamoxifen, and 4′-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patient...

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Bibliographic Details
Published in:Breast cancer research and treatment 2014-02, Vol.143 (3), p.477-483
Main Authors: Jager, N. G. L., Rosing, H., Schellens, J. H. M., Linn, S. C., Beijnen, J. H.
Format: Article
Language:English
Subjects:
Adult
Aged
Ambulatory Care
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cancer research
Cancer therapies
Care and treatment
Chemotherapy
Chromatography, High Pressure Liquid
Clinical Trial
Clinical trials
Dose-Response Relationship, Drug
Drug Monitoring
Female
Health aspects
Humans
Medicine
Medicine & Public Health
Metabolites
Middle Aged
Oncology
Outpatient care facilities
Patients
Tamoxifen
Tamoxifen - administration & dosage
Tamoxifen - analogs & derivatives
Tamoxifen - blood
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Summary:A sensitive and selective HPLC–MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N -desmethyltamoxifen ( E )-endoxifen, ( Z )-endoxifen, N -desmethyl-4′-hydroxytamoxifen, 4-hydroxytamoxifen, and 4′-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the ( Z )-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for ( Z )-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes ( p  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-013-2826-1