Clinical Importance of Plasma Drug Concentration of Oral Molecular Targeted Drugs for Renal Cell Carcinoma

Abstract

Purpose: Therapeutic drug monitoring (TDM) is widely used in clinical practice to maximize drug efficacy and minimize toxicities. Currently, it is also practiced in the use of oral molecular targeted drugs. The objective of this study was to assess the clinical importance of measuring the plasma concentration of oral molecular targeted drugs used to treat renal cell carcinoma (RCC). Methods: The plasma concentrations of the oral molecular targeted drugs sorafenib, sunitinib, axitinib, pazopanib, and everolimus used for RCC were useful for therapeutic interventions, and clinical outcomes were evaluated retrospectively. Results: The interventional use of plasma drug concentration was confirmed in 26 of 87, and their categories are presented. The plasma concentration of sunitinib was useful in dose reduction and/or discontinuation (n = 10), dose escalation (n = 3), and adherence monitoring (n = 2). Nine of the 10 patients whose dose was reduced showed reduced adverse event. Two patients who were intervened in adherence monitor showed improved adherence. For axitinib, dose reduction and/or discontinuation (n = 1) and dose escalation (n = 6) were confirmed. For pazopanib, dose reduction and/or discontinuation (n = 1) and drug interaction detection (n = 1) were confirmed, both of them were confirmed to have reduced adverse events. For everolimus, dose reduction and/or discontinuation (n = 1) and drug interaction detection (n = 1) were confirmed, a patient with reduced dose recovered from adverse events. Interventions for sorafenib were not identified. Conclusions: This study demonstrated that plasma concentrations of oral molecular targeted drugs for RCC were considered to be clinically useful for dose adjustment, monitoring of treatment adherence, and the detection of drug interactions. Moreover, this information could be successfully used to guide individualized therapy to maximize the antitumor effects of these drugs.

Therapeutic Drug Monitoring of Pazopanib in Renal Cell Carcinoma and Soft Tissue Sarcoma: A Systematic Review

“…Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is often used for the TDM of pazopanib. 4,16,38,41,46,51,53,55,[58][59][60] This method is currently the gold standard owing to its excellent specificity. Specifically, the reversed-phase separation method is the most commonly employed TDM method.…”