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

Paul Gougis, Lola-Jade Palmieri, Christian Funck-Brentano, Angelo Paci, Ronan Flippot, Olivier Mir, Romain Coriat

Journal: Critical reviews in oncology/hematology 2019;141():112-124

PMID: 31276964

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Abstract

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.

Address: Sorbonne Université, Faculty of Medicine, AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, F-75013, Paris, France; CLIP² Galilée, Pitié-Salpêtrière Hospital, F-75013, Paris, France. Electronic address: [email protected].; AP-HP, Cochin Hospital, Department of gastroenterology and gastrointestinal oncology, Université Paris Descartes, Paris, France.; Sorbonne Université, Faculty of Medicine, AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology and Clinical Investigation Center, F-75013, Paris, France; INSERM, CIC-1421 and UMR ICAN 1166, Institute of Cardiometabolism and Nutrition (ICAN), F-75013, Paris, France.; Service de Pharmacologie, Département de Biologie et Pathologie Médicales, Gustave Roussy et Université Paris Saclay, Villejuif, France.; Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94800, Villejuif, France.; Department of Medical Oncology, Gustave Roussy, 114 rue Edouard Vaillant, 94800, Villejuif, France; Department of Ambulatory Care, Gustave Roussy Cancer Campus, Villejuif, France.

DOI: 10.1016/j.critrevonc.2019.06.006

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MeSH Terms: Area Under Curve, Biomarkers, Pharmacological, Dose-Response Relationship, Drug, Drug Interactions, Drug Monitoring, Humans, Inactivation, Metabolic, Pharmacology, Clinical, Practice Patterns, Physicians', Protein Kinase Inhibitors, Tissue Distribution