2-C-KJS-3 〇野田 哲史   立命館大学薬学部薬学科医療薬学研究室1 Molecular-targeted therapies using oral multi-kinase inhibitors 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. For example, certain patients treated with oral multi-kinase inhibitors at standard doses have severe adverse effects and require dose reduction and discontinuation, yet other patients have a suboptimal response to these drugs. Consequently, optimizing the dosing of oral multi-kinase inhibitors is important to prevent over-dosing or under-dosing. To date, multiple studies on the exposure-efficacy/toxicity relationship of molecular targeted therapy have been attempted for the implementation of therapeutic drug monitoring (TDM) strategies. In this situation, we recently conducted research on several multi-kinase inhibitors with the aim to optimize their treatment efficacy using a PK/PD approach. Among them, sunitinib use is an example of successful TDM implementation. Sunitinib demonstrated a significant correlation between drug exposure and treatment efficacy or toxicities. As a result, TDM services for sunitinib has been covered by the National Health Insurance program in Japan since April 2018. Additionally, other multi-kinase targeted anticancer drugs have promising data regarding the exposure-efficacy/toxicity relationship, suggesting the possibility of personalization of drug dosage. In this lecture, we provide a comprehensive summary of the clinical evidence for dose individualization of multi-kinase inhibitors and discuss the utility of TDM of multi-kinase inhibitors.
1)Noda et al., Biol. Pharm. Bull. 45, 814-823, 2022