Association of pharmacokinetics of axitinib with treatment outcome and adverse events in advanced renal cell carcinoma patients.

Abstract

506 Background: Therapeutic drug monitoring (TDM) has been recognized as a useful tool for optimizing the dose of many drugs. The effectiveness of TDM for molecular targeted agents, however, has not so far been established. In this study, we examined the associations between pharmacokinetics of axitinib (AXI) and adverse events (AEs) and clinical outcomes in patients with advanced renal cell carcinoma (aRCC). Methods: The pharmacokinetics of AXI was examined in 24 patients (18 males and 6 females) with aRCC. The plasma AXI levels were measured using high-performance liquid chromatography and a pharmacokinetic study was performed on day 7 in the first cycle. Subsequently, the associations between the pharmacokinetics of AXI and the occurrence and grade of AEs, best tumor response, and progression-free survival (PFS) were investigated. Results: All the patients were been treated with 10 mg/day of AXI at the day of pharmacokinetics and the trough levels were ranged between 1.2 and 70.97 ng/mL. The trough levels were significantly associated with the occurrence of hypertension, hyperthyroidism, and grade 1 or higher proteinuria (p=0.037, 0.024, 0.027 by Mann-Whitney test, respectively), and were associated with the best tumor response (by Mann-Whitney test, p=0.043) (Table 1). Patients with 5.0 ng/mL of higher trough levels of AXI showed a tendency toward longer PFS than those with the trough levels less than 5.0 ng/mL (Table 2). Conclusions: TDM of AXI in patients with aRCC may be useful to determine the adequate dose and prevent severe AEs. Further studies are mandatory to conclude the usefulness of TDM of AXI for the long-term clinical efficacy in patients with aRCC. [Table: see text] [Table: see text]