PMID- 31538342
OWN - NLM
STAT- MEDLINE
DCOM- 20210211
LR  - 20210211
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 60
IP  - 2
DP  - 2020 Feb
TI  - Pharmacokinetics of Neoadjuvant Axitinib Influenced the Efficacy in Patients With 
      Advanced Renal Cell Carcinoma.
PG  - 256-263
LID - 10.1002/jcph.1521 [doi]
AB  - Although axitinib shows a good objective response rate and acceptable 
      tolerability for advanced renal cell carcinoma, substantial differences in drug 
      concentrations among individuals have hampered the reliable administration of the 
      drug in a neoadjuvant setting. This study aimed to evaluate the relationship 
      between axitinib pharmacokinetics and clinical efficacy in patients with advanced 
      renal cell carcinoma treated in a neoadjuvant setting. We retrospectively 
      reviewed 16 patients who underwent neoadjuvant axitinib treatment from 
      prospective phase 2 study cohorts treated with axitinib and assessed whether the 
      drug concentration was associated with clinical efficacy for primary tumors of 
      advanced metastatic/oligometastatic clear cell renal cell carcinoma. Axitinib was 
      administered orally at a starting dose of 5 mg twice daily for 2 months in 
      principle before the operation, and the axitinib pharmacokinetics were examined. 
      Best response, reduction rate, adverse events (AEs), and surgical complication 
      were assessed. Four patients (25.0%) showed a partial response, and 12 (75.0%) 
      had stable disease, with a mean reduction rate of 22.8%. No progressive disease 
      was noted, and 9 of the 16 patinets (56.3%) showed downstaging. The trough level 
      of axitinib significantly correlated with the objective response rate (P = .0052) 
      and best tumor reduction (P = .0128). All AEs could be safely managed until 
      termination of the dosing period. With respect to perioperative complications, 
      grade 2 anemia was observed. Neoadjuvant axitinib treatment showed acceptable 
      antitumor activity and safety profile for advanced renal cell carcinoma. The 
      pharmacokinetics of neoadjuvant axitinib influenced the efficacy in patients with 
      advanced renal cell carcinoma.
CI  - (c) 2019, The American College of Clinical Pharmacology.
FAU - Yamamoto, Yoshiaki
AU  - Yamamoto Y
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
FAU - Otori, Toru
AU  - Otori T
AD  - Faculty of Pharmacy, Kindai University, Higashiosaka, Osaka, Japan.
FAU - Inoue, Ryo
AU  - Inoue R
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
FAU - Yano, Seiji
AU  - Yano S
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
FAU - Hirata, Hiroshi
AU  - Hirata H
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
FAU - Matsumoto, Hiroaki
AU  - Matsumoto H
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
FAU - Matsuyama, Kenji
AU  - Matsuyama K
AD  - Faculty of Pharmacy, Daiichi College of Pharmaceutical Sciences, Fukuoka, 
      Fukuoka, Japan.
FAU - Matsuyama, Hideyasu
AU  - Matsuyama H
AD  - Department of Urology, Graduate School of Medicine, Yamaguchi University, Ube, 
      Yamaguchi, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190919
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antineoplastic Agents)
RN  - C9LVQ0YUXG (Axitinib)
RN  - Clear-cell metastatic renal cell carcinoma
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/*pharmacokinetics
MH  - Axitinib/adverse effects/*pharmacokinetics
MH  - Carcinoma, Renal Cell/*drug therapy/surgery
MH  - Clinical Trials, Phase II as Topic
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/surgery
MH  - Male
MH  - Middle Aged
MH  - Neoadjuvant Therapy/adverse effects
MH  - Retrospective Studies
MH  - Treatment Outcome
OTO - NOTNLM
OT  - VEGFR-TKI
OT  - antitumor activity
OT  - neoadjuvant axitinib
OT  - pharmacokinetics
OT  - renal cell carcinoma
EDAT- 2019/09/21 06:00
MHDA- 2021/02/12 06:00
CRDT- 2019/09/21 06:00
PHST- 2019/05/24 00:00 [received]
PHST- 2019/08/16 00:00 [accepted]
PHST- 2019/09/21 06:00 [pubmed]
PHST- 2021/02/12 06:00 [medline]
PHST- 2019/09/21 06:00 [entrez]
AID - 10.1002/jcph.1521 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2020 Feb;60(2):256-263. doi: 10.1002/jcph.1521. Epub 2019 Sep 
      19.