Population Pharmacokinetics of Docetaxel, Paclitaxel, Doxorubicin and Epirubicin in Pregnant Women with Cancer: A Study from the International Network of Cancer, Infertility and Pregnancy (INCIP)

Autor: Ingrid A. Boere, Robert Fruscio, Jos H. Beijnen, Petronella O. Witteveen, Carolien P. Schröder, Rebecca C. Painter, Alwin D. R. Huitema, Petronella B. Ottevanger, Frédéric Amant, Julie M Janssen, Vit Drochytek, Thomas P. C. Dorlo, Michael J. Halaska, Ruud L.M. Bekkers, Kristel Van Calsteren
Přispěvatelé: Guided Treatment in Optimal Selected Cancer Patients (GUTS), Janssen, J, Van Calsteren, K, Dorlo, T, Halaska, M, Fruscio, R, Ottevanger, P, Schroder, C, Boere, I, Witteveen, P, Painter, R, Bekkers, R, Drochytek, V, Beijnen, J, Huitema, A, Amant, F, Obstetrics and Gynaecology, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, ARD - Amsterdam Reproduction and Development, CCA - Cancer biology and immunology, Medical Oncology, RS: GROW - R2 - Basic and Translational Cancer Biology, Obstetrie & Gynaecologie
Rok vydání: 2021
Předmět:
Zdroj: Clinical Pharmacokinetics, 60, 6, pp. 775-784
Clinical Pharmacokinetics
Clinical Pharmacokinetics, 60, 775-784
Clinical Pharmacokinetics. Springer International Publishing AG
Clinical pharmacokinetics, 60(6), 775-784. Adis International Ltd
Clinical Pharmacokinetics, 60(6), 775-784. Adis
Clinical Pharmacokinetics, 60(6), 775-784. Adis International Ltd
ISSN: 0312-5963
Popis: BACKGROUND: Based on reassuring short-term foetal and maternal safety data, there is an increasing trend to administer chemotherapy during the second and third trimesters of pregnancy. The pharmacokinetics (PK) of drugs might change as a result of several physiological changes that occur during pregnancy, potentially affecting the efficacy and safety of chemotherapy. OBJECTIVE: With this analysis, we aimed to quantitatively describe the changes in the PK of docetaxel, paclitaxel, doxorubicin and epirubicin in pregnant women compared with non-pregnant women. METHODS: PK data from 9, 20, 22 and 16 pregnant cancer patients from the International Network of Cancer, Infertility and Pregnancy (INCIP) were available for docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. These samples were combined with available PK data from non-pregnant patients. Empirical non-linear mixed-effects models were developed, evaluating fixed pregnancy effects and gestational age as covariates. RESULTS: Overall, 82, 189, 271, and 227 plasma samples were collected from pregnant patients treated with docetaxel, paclitaxel, doxorubicin and epirubicin, respectively. The plasma PK data were adequately described by the respective models for all cytotoxic drugs. Typical increases in central and peripheral volumes of distribution of pregnant women were identified for docetaxel, paclitaxel, doxorubicin and epirubicin. Additionally, docetaxel, doxorubicin and paclitaxel clearance were increased in pregnant patients, resulting in lower exposure in pregnant women compared with non-pregnant patients. CONCLUSION: Given the interpatient variability, the identified pregnancy-induced changes in PK do not directly warrant dose adjustments for the studied drugs. Nevertheless, these results underscore the need to investigate the efficacy of chemotherapy, when administered during pregnancy. ispartof: CLINICAL PHARMACOKINETICS vol:60 issue:6 pages:775-784 ispartof: location:Switzerland status: published
Databáze: OpenAIRE
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