Molecular-targeted therapy in advanced renal cell carcinoma based on pharmacokinetics, pharmacodynamics and pharmacogenetics: A proposed strategy.

Abstract

In advanced renal cell carcinoma, a transition of drug therapies from cytokines to molecular-targeted drugs and immune-oncology drugs provides more clinical benefits to patients, while adequate management is required for various and sometimes serious adverse events. At present, the relationship between the pharmacokinetics of many drugs and their effectiveness or adverse events has been elucidated, and therapeutic drug monitoring is being applied to some immunosuppressive, anti-epileptic and antibacterial drugs in daily clinical practice. Most of the molecular-targeted drugs used in patients with renal cell carcinoma are orally active, and are affected by absorption and disposition, which can be different for each individual. The monitoring of the circulating drug concentration could be beneficial to patients by providing information for the adjustment of drug dose and the maintenance of a therapeutic plasma concentration range. Genetic polymorphisms are known to be involved in pharmacokinetics, and cause individual differences in clinical efficacy and adverse events. Therefore, a more scientific strategy should be used in regard to the treatment of patients with advanced renal cell carcinoma treated with molecular-targeted drugs by accumulating evidence on pharmacodynamics and pharmacogenetics.