1. Pronounced Interindividual But Not Intraindividual Variation in Tamoxifen and Metabolite Levels in Plasma During Adjuvant Treatment of Women With Early Breast Cancer
- Author
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Pierre Lafolie, Jennie Östervall, Anton Pohanka, Alan Kambiz Fotoohi, Sigurd Vitols, Hazhar Karim, and Thomas Hatschek
- Subjects
Drug ,Oncology ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,medicine.drug_class ,media_common.quotation_subject ,Metabolite ,medicine.medical_treatment ,Breast Neoplasms ,Pharmacology ,030226 pharmacology & pharmacy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Tandem Mass Spectrometry ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,Chromatography, High Pressure Liquid ,Aged ,media_common ,Early breast cancer ,Estradiol ,business.industry ,Luteinizing Hormone ,medicine.disease ,Tamoxifen ,chemistry ,Estrogen ,030220 oncology & carcinogenesis ,Female ,Follicle Stimulating Hormone ,business ,Adjuvant ,medicine.drug ,Clearance - Abstract
Tamoxifen is still an important antihormonal treatment option for patients with breast cancer and estrogen receptor-positive tumors. More than 20% of patients relapse despite treatment. The drug is usually dosed 20 mg/d irrespective of interindividual variation in drug clearance. To study interindividual and intraindividual variation in plasma levels we measured tamoxifen and metabolite levels in plasma on 2 occasions, with at least 4 weeks in between, of 39 women (19 premenopausal and 20 postmenopausal women) on adjuvant treatment (20 mg/d) of early breast cancer.We used an ultra-performance liquid chromatography with a mass spectrometry detection method for identification and quantification of tamoxifen, N-desmethyltamoxifen, 4-OH-tamoxifen, and endoxifen. Follicle-stimulating hormone, luteinizing hormone, and estradiol levels were also measured.The plasma concentrations of tamoxifen and its metabolites showed a pronounced interindividual variation, whereas intraindividual concentrations were rather stable. Despite the same dosage, interindividual tamoxifen concentrations varied from 51 to 307 ng/mL (124 ± 57, mean ± SD) and endoxifen values showed a range from 3.2 to 19 ng/mL (10.4 ± 5.2, mean ± SD), that is, 6-fold variation for both.Large interindividual variation of tamoxifen and endoxifen with stable intraindividual levels, and too low levels of endoxifen in a considerable proportion of patients strongly support that therapeutic drug monitoring and individualized dosing could lead to optimal exposure and hopefully better outcome. A randomized outcome study between conventional dosing and therapeutic drug monitoring-guided dosing is needed to show whether this approach works.
- Published
- 2016
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