MP16-01 CLINICAL IMPLICATIONS OF SUNITINIB AND N-DESETHYL-SUNITINIB PLASMA CONCENTRATIONS FOR TREATMENT OUTCOME IN METASTATIC RENAL CELL CARCINOMA PATIENTS

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) II1 Apr 2017MP16-01 CLINICAL IMPLICATIONS OF SUNITINIB AND N-DESETHYL-SUNITINIB PLASMA CONCENTRATIONS FOR TREATMENT OUTCOME IN METASTATIC RENAL CELL CARCINOMA PATIENTS Kazuyuki Numakura, Nobuhiro Fujiyama, Makoto Takahashi, Hiroshi Tsuruta, Atsushi Maeno, Mitsuru Saito, Takamitsu Inoue, Shintaro Narita, Mingguo Huang, Shigeru Satoh, Takenori Niioka, Masatomo Miura, and Tomonori Habuchi Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Nobuhiro FujiyamaNobuhiro Fujiyama More articles by this author , Makoto TakahashiMakoto Takahashi More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Atsushi MaenoAtsushi Maeno More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , Takenori NiiokaTakenori Niioka More articles by this author , Masatomo MiuraMasatomo Miura More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.507AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Therapeutic drug monitoring (TDM) has been recognized as a useful tool for optimizing the dosages of many drugs, even in molecular-targeted therapeutics. In this study, we examined the associations between the pharmacokinetics of sunitinib (SU) and its metabolite N-desethyl-sunitinib (DSU) and adverse events (AEs) and clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). METHODS The pharmacokinetics of SU and DSU were examined in 26 patients (20 male and 6 female patients) with mRCC. Plasma SU and DSU levels were measured using high-performance liquid chromatography, and a pharmacokinetic study was performed on day 7 in the first cycle of SU. The associations between SU/DSU pharmacokinetics and the occurrence of AEs, best response rate, progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS) were investigated. RESULTS All patients were treated with 37.5 mg/day SU at the day of pharmacokinetics. The mean trough levels of SU and DSU were 76.7 and 16.8 ng/mL respectively. Occurrence of hand-foot syndrome and thrombocytopenia (P = 0.002 and 0.024 respectively by Mann-Whitney test) was associated with high trough levels of SU. Low trough levels of DSU were significantly associated with drug discontinuation due to disease progression and were associated with worse tumor response (P = 0.035 and 0.042 respectively by Mann-Whitney test, Figure 1). Patients with DSU trough levels of or higher than 15.0 ng/mL showed a tendency toward increased PFS, TTF, and OS than those with trough levels lower than 15.0 ng/mL (Figure 2). SU trough levels were not associated with prognosis. CONCLUSIONS TDM of SU and DSU in patients with mRCC may be useful to determine adequate dosages and prevent severe AEs. Further studies are required to establish the usefulness of TDM of SU and DSU for ensuring long-term clinical efficacy in patients with mRCC. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e179 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kazuyuki Numakura More articles by this author Nobuhiro Fujiyama More articles by this author Makoto Takahashi More articles by this author Hiroshi Tsuruta More articles by this author Atsushi Maeno More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Shintaro Narita More articles by this author Mingguo Huang More articles by this author Shigeru Satoh More articles by this author Takenori Niioka More articles by this author Masatomo Miura More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...