A pharmacometrics model to define docetaxel target in early breast cancer.
breast cancer
docetaxel
pharmacodynamics
pharmacokinetics
precision medicine
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
23
08
2022
received:
21
03
2022
accepted:
01
09
2022
pubmed:
14
9
2022
medline:
18
1
2023
entrez:
13
9
2022
Statut:
ppublish
Résumé
We aimed to study the relation between pharmacokinetics (PK) and pharmacodynamics (PD) of docetaxel in early breast cancer and recommend a target exposure. A PK/PD study was performed in 27 early breast cancer patients treated with doxorubicin and cyclophosphamide for 4 cycles followed by 4 cycles of docetaxel 75-100 mg/m Docetaxel clearance showed no change over the 4 treatment cycles, but a gradual increase in the volume of distribution was observed. One third of the patients had at least 1 dose reduction of docetaxel due to toxicity. The mean AUC, AUCcum and Cmax in patients showing docetaxel-associated adverse events were significantly higher than in patients free of toxicity (P < .05). Fatigue and decrease in haemoglobin and haematocrit levels were related to docetaxel AUC and Cmax and pain to AUC. AUC and Cmax >4.5 mg*h/L and 3.5 mg/L, respectively, were risk factors for docetaxel toxicity, while an AUC <4.5 mg*h/L was associated with tumour recurrence. We report for the first time a relation between docetaxel exposure and toxicity and recommend specific targets of drug exposure with implications for the clinical management of early breast cancer patients.
Identifiants
pubmed: 36098504
doi: 10.1111/bcp.15526
pmc: PMC10087179
doi:
Substances chimiques
Docetaxel
15H5577CQD
Taxoids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
727-736Informations de copyright
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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