Exposure-response analysis of endoxifen serum concentrations in early-breast cancer
| Autor: | Henk-Jan Guchelaar, Hans Gelderblom, Diether Lambrechts, Vincent O. Dezentjé, D J A R Moes, A B Sanchez-Spitman, Jesse J. Swen, Patrick Neven |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Antineoplastic Agents Hormonal Breast Neoplasms Toxicology Endoxifen TDM Breast cancer Internal medicine medicine Humans Pharmacology (medical) Prospective Studies Pharmacology medicine.diagnostic_test Proportional hazards model business.industry Clinical outcome Hazard ratio Odds ratio Middle Aged medicine.disease Prognosis Confidence interval Discontinuation Survival Rate Tamoxifen Therapeutic drug monitoring Original Article Female Drug Monitoring business medicine.drug Follow-Up Studies |
| Zdroj: | Cancer Chemotherapy and Pharmacology Cancer Chemotherapy and Pharmacology, 85(6), 1141-1152. SPRINGER |
| Popis: | Purpose Tamoxifen is part of endocrine therapy in breast cancer treatment. Studies have indicated the use of endoxifen concentrations, tamoxifen active metabolite, to guide tamoxifen efficacy. Three endoxifen thresholds have been suggested (5.9 ng/ml, 5.2 ng/ml and 3.3 ng/ml) for therapeutic drug monitoring (TDM). Our aim was to validate these thresholds and to examine endoxifen exposure with clinical outcome in early-breast cancer patients using tamoxifen. Methods Data from 667 patients from the CYPTAM study (NTR1509) were available. Patients were stratified (above or below), according to the endoxifen threshold values for tamoxifen efficacy and tested by Cox regression. Logistic regressions to estimate the probability of relapse and tamoxifen discontinuation were performed. Results None of the thresholds showed a statistically significant difference in relapse-free survival: 5.2 ng/ml threshold: hazard ratio (HR): 2.545, 95% confidence interval (CI) 0.912–7.096, p value: 0.074; 3.3 ng/ml threshold: HR: 0.728; 95% CI 0.421–1.258, p value: 0.255. Logistic regression did not show a statistically significant association between the risk of relapse (odds ratio (OR): 0.971 (95% CI 0.923–1.021, p value: 0.248) and the risk for tamoxifen discontinuation (OR: 1.006 95% CI 0.961–1.053, p value: 0.798) with endoxifen concentrations. Conclusion Our findings do not confirm the endoxifen threshold values for TDM nor does it allow definition of a novel threshold. These findings indicate a limited value of TDM to guide tamoxifen efficacy. |
| Databáze: | OpenAIRE |
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