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Master Thesis

Étude de l’association entre la concentration plasmatique, la tolérance et l’efficacité du Sorafénib, chez les patients débutant un traitement palliatif pour carcinome hépatocellulaire

Abstract : Background and Aim: Sorafenib, an oral multi-kinase inhibitor, is indicated as a first-line palliative treatment for advanced hepatocellular carcinoma (HCC). The impact on patient survival is low and the adverse effect are common leading to many therapeutic interruptions. Currently, there are no factors to predict the safety or efficacy of treatment but several studies have suggested a significant impact of pharmacokinetics. The objective of this study was to evaluate the association between pharmacokinetics of Sorafenib and the adverse effects. Methods: 114 patients were enrolled in this multicenter prospective study and 60 patients received a S4 plasma concentration assay without prior dose adjustment. The collection of AEs was conducted at follow-up consultations at S4, S8 and S16. Results: of the 60 patients, a total of 36 (60%) and 9(15%) patient experienced respectively grade 2 and 3– 4 toxicities. The mean Sorafénib concentration was 4725.28ng / mL with high interindividual variability. The mean Sorafénib concentration in patients with a grade III toxicities was significantly higher than in the other patients (p = 0.0218). In multivariate analysis, no factor other than the concentration appeared to be associated with the occurrence of grade III toxicities (p=0,06). Conclusion: the association between Sorafenib concentration and tolerance can make discuss a monitoring of the treatment. This could have a major impact on clinical management by limiting the adverse effects impacting the quality of life of these fragile patients.
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https://dumas.ccsd.cnrs.fr/dumas-02431960
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Submitted on : Wednesday, January 8, 2020 - 11:40:41 AM
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Caroline Toulouse. Étude de l’association entre la concentration plasmatique, la tolérance et l’efficacité du Sorafénib, chez les patients débutant un traitement palliatif pour carcinome hépatocellulaire. Sciences du Vivant [q-bio]. 2019. ⟨dumas-02431960⟩

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