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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Molecular-targeted therapy in advanced renal cell carcinoma based on pharmacokinetics, pharmacodynamics and
1Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.
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.
Insights
Monitoring drug levels in advanced renal cell carcinoma patients can personalize treatment. This approach optimizes molecular-targeted drug doses, improving efficacy and managing adverse events for better patient outcomes.
Area of Science:
- Pharmacology and Oncology
- Translational Medicine
- Clinical Pharmacy
Background:
- Advanced renal cell carcinoma treatment has shifted from cytokines to molecular-targeted and immune-oncology drugs.
- Managing diverse and severe adverse events associated with these therapies is crucial.
- Pharmacokinetics and therapeutic drug monitoring (TDM) are established for certain drug classes.
Purpose of the Study:
- To explore the potential benefits of monitoring circulating drug concentrations for oral molecular-targeted drugs in advanced renal cell carcinoma.
- To investigate how TDM can aid in dose adjustment and maintaining therapeutic plasma concentrations.
- To highlight the role of pharmacogenetics in individualizing treatment strategies.
Main Methods:
- Review of current literature on pharmacokinetics, pharmacodynamics, and pharmacogenetics of molecular-targeted drugs in renal cell carcinoma.
- Analysis of the impact of individual absorption and disposition variability on drug efficacy and safety.
- Discussion on the application of TDM principles to molecular-targeted therapies.
Main Results:
- Oral molecular-targeted drugs in renal cell carcinoma are subject to significant inter-individual pharmacokinetic variability.
- Monitoring drug concentrations can provide actionable insights for dose optimization and therapeutic range maintenance.
- Genetic polymorphisms significantly influence drug pharmacokinetics, leading to varied clinical responses and adverse events.
Conclusions:
- Therapeutic drug monitoring of circulating concentrations is a promising strategy for optimizing molecular-targeted therapy in advanced renal cell carcinoma.
- Integrating pharmacodynamic and pharmacogenetic data can lead to more scientific and personalized treatment approaches.
- Further research is needed to establish evidence-based TDM protocols for these agents.
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