Major pitfalls of protein kinase inhibitors prescription: a review of their clinical pharmacology for daily use

Paul Gougis (1, 2) , Lola-Jade Palmieri (3, 4) , Christian Funck-Brentano (5, 1, 2) , Angelo Paci (6, 7, 8) , Ronan Flippot (9) , Olivier Mir (9, 10) , Romain Coriat (11)

1 CHU Pitié-Salpêtrière [AP-HP]
2 SU FM - Sorbonne Université - Faculté de Médecine
3 Hôpital Cochin [AP-HP]
4 UPD5 - Université Paris Descartes - Paris 5
5 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
6 Université Paris-Saclay
7 Département de biologie et pathologie médicales [Gustave Roussy]
8 UMR 1030 - Radiothérapie moléculaire
9 Département de médecine oncologique [Gustave Roussy]
10 Département ambulatoire [Gustave Roussy]
11 Service de Gastro-entérologie [CHU Cochin]

Protein kinase inhibitors (PKI) are a growing class of anticancer agents. They are prescribed with flat doses, and their oral administration is associated with interindividual variability in exposure. Patients can be over- or underexposed, due to numerous factors. We reviewed key pharmacokinetic concepts and mechanisms by which PKIs prescription could be altered. Challenging situations that could lead to increased toxicity or to therapeutic failure are described and recommendation for clinicians are proposed. Finally, the interest of therapeutic drug monitoring and indications for its use in daily practice is discussed.

Mots clés: Cancer treatment; Pharmacology; Therapeutic drug monitoring; Protein kinase inhibitors

Domaines: Pharmacologie; Cancer

Paul Gougis, Lola-Jade Palmieri, Christian Funck-Brentano, Angelo Paci, Ronan Flippot, et al.. Major pitfalls of protein kinase inhibitors prescription: a review of their clinical pharmacology for daily use. Critical Reviews in Oncology/Hematology, 2019, 141, pp.112-124. ⟨10.1016/j.critrevonc.2019.06.006⟩. ⟨hal-02289357⟩