PMID- 29861870
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 38
DP  - 2018 May 18
TI  - Clinical implications of pharmacokinetics of sunitinib malate and 
      N-desethyl-sunitinib plasma concentrations for treatment outcome in metastatic 
      renal cell carcinoma patients.
PG  - 25277-25284
LID - 10.18632/oncotarget.25423 [doi]
AB  - In this study, we examined the association between the pharmacokinetics (PK) 
      level of sunitinib malate (SU) and its metabolite N-desethyl-sunitinib (DSU) in 
      terms of adverse events (AEs) and clinical outcomes in patients with metastatic 
      renal cell carcinoma (mRCC). The PK of sunitinib (SU and DSU) was examined in 26 
      patients (20 men and 6 women) with mRCC. The associations between SU/DSU C0 and 
      AE occurrence, best response rate, time to treatment failure, progression-free 
      survival (PFS), and overall survival (OS) were investigated. Occurrence of grade 
      1 or higher hand-foot syndrome and thrombocytopenia (p = 0.002 and 0.024, 
      respectively) was associated with a high concentration before morning intake (C0) 
      level of SU. Low C0 levels of DSU were significantly associated with drug 
      discontinuation due to disease progression (p = 0.035). Patients with DSU C0 
      level higher than 15.0 ng/mL showed a tendency toward increased PFS (61 weeks vs 
      12 weeks, p = 0.004) and OS (36 months vs 8 months, p = 0.040). The C0 level of 
      SU and SU + DSU were not associated with prognosis. The higher level of C0 of SU 
      may predict developing AEs and DSU C0 >15.0 ng/mL may lead to better prognosis of 
      patients treated with sunitinib. PK of sunitinib may be useful for determining 
      adequate dosages and prevention of severe AEs. Further studies are required to 
      establish the utility of the PK of sunitinib in patients with mRCC.
FAU - Numakura, Kazuyuki
AU  - Numakura K
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Fujiyama, Nobuhiro
AU  - Fujiyama N
AD  - Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, 
      Japan.
FAU - Takahashi, Makoto
AU  - Takahashi M
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Igarashi, Ryoma
AU  - Igarashi R
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Tsuruta, Hiroshi
AU  - Tsuruta H
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Maeno, Atsushi
AU  - Maeno A
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Huang, Mingguo
AU  - Huang M
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Saito, Mitsuru
AU  - Saito M
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Narita, Shintaro
AU  - Narita S
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Inoue, Takamitsu
AU  - Inoue T
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Satoh, Shigeru
AU  - Satoh S
AD  - Center for Kidney Disease and Transplantation, Akita University Hospital, Akita, 
      Japan.
FAU - Tsuchiya, Norihiko
AU  - Tsuchiya N
AD  - Department of Urology, Yamagata University, Faculty of Medicine, Yamagata, Japan.
FAU - Niioka, Takenori
AU  - Niioka T
AD  - Division of Pharmaceutical Science, Akita University Hospital, Akita, Japan.
FAU - Miura, Masatomo
AU  - Miura M
AD  - Division of Pharmaceutical Science, Akita University Hospital, Akita, Japan.
FAU - Habuchi, Tomonori
AU  - Habuchi T
AD  - Department of Urology, Akita University Graduate School of Medicine, Akita, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20180518
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5982748
OTO - NOTNLM
OT  - N-desethyl-sunitinib
OT  - pharmacokinetics
OT  - renal cell carcinoma
OT  - sunitinib
COIS- CONFLICTS OF INTEREST Drs. Habuchi, Satoh and Tsuchiya received honoraria from 
      Novartis Pharma. Drs. Habuchi and Tsuchiya received honoraria from Pfizer Co. Dr. 
      Habuchi received honoraria from and GlaxoSmithKline.
EDAT- 2018/06/05 06:00
MHDA- 2018/06/05 06:01
PMCR- 2018/05/18
CRDT- 2018/06/05 06:00
PHST- 2017/12/01 00:00 [received]
PHST- 2018/05/01 00:00 [accepted]
PHST- 2018/06/05 06:00 [entrez]
PHST- 2018/06/05 06:00 [pubmed]
PHST- 2018/06/05 06:01 [medline]
PHST- 2018/05/18 00:00 [pmc-release]
AID - 25423 [pii]
AID - 10.18632/oncotarget.25423 [doi]
PST - epublish
SO  - Oncotarget. 2018 May 18;9(38):25277-25284. doi: 10.18632/oncotarget.25423. 
      eCollection 2018 May 18.