Cetuximab pharmacokinetic/pharmacodynamics relationships in advanced head and neck carcinoma patients

British Journal of Clinical Pharmacology
Félicien Le LouedecFabienne Thomas

Abstract

Cetuximab associated with cisplatin and 5-fluorouracil is used to treat patients with inoperable or metastatic head and neck squamous cell carcinomas (HNSCC) up until disease progression or unacceptable toxicities. To date, no biomarkers of efficacy are available to select patients who will benefit from treatment. An ancillary pharmacokinetics (PK) exploration was performed in the context of a prospective study investigating circulating-tumour cells vs progression-free survival (PFS). Cetuximab plasma concentrations were analysed according to a population PK model. Individual exposure parameters were confronted with soluble epidermal growth factor receptor (sEGFR) concentrations, tumour response and PFS. PK data (28 patients, 203 observations) were best described by a two-compartment model with linear elimination. Performance status (PS) significantly correlated to both cetuximab clearance and central volume of distribution with both parameters increasing by 33.3% (95% CI 1-65.6) for each 1-point increase of PS compared to PS = 0. Univariate analysis showed that patients with higher trough cetuximab concentrations at Day 7 (Cmin,D7 ) had better tumour response (P = 0.03) and longer PFS (P = 0.035). However, multivariate analysi...Continue Reading

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Citations

Aug 8, 2019·Clinical Chemistry·Klaus Pantel
Nov 9, 2019·Clinical Pharmacokinetics·Etienne ChatelutGérard Milano
Aug 21, 2020·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Nádia Ghinelli AmôrCamila Oliveira Rodini
Jun 20, 2020·Clinical Pharmacology and Therapeutics·Florent FerrerJoseph Ciccolini
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Jun 22, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Silvia Peña-CabiaAna López-Martín

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