In Asia, molecular-targeted therapies using tyrosine kinase inhibitors (TKIs) have achieved a significant increase in the overall survival of cancer patients. These agents are mainly administrated orally at a fixed dose, which often causes large interindividual variability of clinical pharmacokinetic and/or pharmacodynamic (PK/PD) parameters. In particular, Asian patients experience more drug toxicity in response to certain TKIs compared to non-Asian patients. This often results in dose reduction or complete termination of treatment, which has initiated efforts to optimize the dosing schedule to improve drug tolerance. To address these issues, therapeutic drug monitoring has been applied in clinical settings. This review article summarizes the pharmacological factors that are known to cause variations in PK/PD parameters, such as genetic polymorphisms of metabolic enzymes and transporters and drug–drug interactions. This review also discusses the possibility of dose individualization in Asian patients during TKI therapy, primarily focusing on sunitinib or pazopanib.
Keywords: tyrosine kinase inhibitors, individual dosing, therapeutic drug monitoring, Asians
