Tyrosine kinase inhibitors in cancers: Treatment optimization – Part II

Real-life populations are more heterogeneous than those included in prospective clinical studies. In cancer patients, comorbidities and co-medications favor the appearance of severe adverse effects which can significantly impact quality of life and treatment effectiveness. Most of tyrosine kinase inhibitors (TKI) have been developed with flat oral dosing exposing patients to the risk of poor adherence due to side effects. Additionally, genetic or physiological factors, differences in diet, and drug-drug interactions can lead to inter-individual variability affecting treatment outcomes and increasing the risk of adverse events. Knowledge of the different factors of variability allows individualized patient management. This review examines the effects of adherence, food intake, and pharmaceutical form on the pharmacokinetics of oral TKI, as well as evaluating pharmacokinetics considerations improving TKI management. Concentration-effectiveness and concentration-toxicity data are presented for the selected TKI, and a simple therapeutic drug monitoring schema is outlined to help individualize dosing of oral TKI. •Flat oral dosing of TKI takes no consideration of heterogeneity among cancer patients and can promote non-adherence.•Genetic or physiological factors, diet, and drug–drug interactions lead to PK variability.•Use of exposure–effect data to individualize treatment can ensure optimized outcomes and reduced toxicity.•Therapeutic drug monitoring can help to further individualize dosing of oral TKI.