PMID- 29577674
OWN - NLM
STAT- MEDLINE
DCOM- 20190906
LR  - 20240314
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 7
IP  - 5
DP  - 2018 May
TI  - A phase 4 study of nilotinib in Korean patients with Philadelphia 
      chromosome-positive chronic myeloid leukemia in chronic phase: ENESTKorea.
PG  - 1814-1823
LID - 10.1002/cam4.1450 [doi]
AB  - Although nilotinib has improved efficacy compared to imatinib, suboptimal 
      response and intolerable adverse events (AEs) limit its effectiveness in many 
      patients with chronic myeloid leukemia in chronic phase (CML-CP). We investigated 
      the 2-year efficacy and safety of nilotinib and their relationships with plasma 
      nilotinib concentrations (PNCs). In this open-label, multi-institutional phase 4 
      study, 110 Philadelphia chromosome-positive CML-CP patients were treated with 
      nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and 
      AEs were monitored for up to 24 months. The 24-month cumulative MR(4.5) rate was 
      evaluated as the primary endpoint. Plasma samples were collected from 94 patients 
      to determine PNCs, and the per-patient mean was used to categorize them into four 
      mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between 
      groups. With a median follow-up of 22.2 months, the 24-month cumulative MR(4.5) 
      rate was 56.2% (95% confidence interval, 44.0%-8.3%), and the median time to 
      MR(4.5) was 23.3 months. There were no significant differences in the cumulative 
      rates of major molecular response, MR(4) , and MR(4.5) between MPNC groups. One 
      patient died due to acute viral hepatitis, and two developed hematological or 
      cytogenetic relapse, while no progression to accelerated or blast phase was 
      observed. Safety results were consistent with previous studies with no new safety 
      signal identified. Across the MPNC groups, there was no significant linear trend 
      in the frequency of AEs. Nilotinib is highly effective for the treatment of 
      CML-CP with manageable AEs. The measurement of PNC has no predictive value for 
      patient outcomes and is thus not found to be clinically useful. This study is 
      registered with clinicaltrials.gov, Number NCT03332511.
CI  - (c) 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Shin, Junghoon
AU  - Shin J
AUID- ORCID: 0000-0002-6834-7217
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, Korea.
FAU - Koh, Youngil
AU  - Koh Y
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, Korea.
FAU - Yoon, Seo Hyun
AU  - Yoon SH
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul, Korea.
FAU - Cho, Joo-Youn
AU  - Cho JY
AD  - Department of Clinical Pharmacology and Therapeutics, Seoul National University 
      Hospital, Seoul, Korea.
FAU - Kim, Dae-Young
AU  - Kim DY
AD  - Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
FAU - Lee, Kyoo-Hyung
AU  - Lee KH
AD  - Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
FAU - Kim, Hyeong-Joon
AU  - Kim HJ
AD  - Department of Internal Medicine, Chonnam National University Hwasun Hospital, 
      Hwasun, Korea.
FAU - Ahn, Jae-Sook
AU  - Ahn JS
AD  - Department of Internal Medicine, Chonnam National University Hwasun Hospital, 
      Hwasun, Korea.
FAU - Kim, Yeo-Kyeoung
AU  - Kim YK
AD  - Department of Internal Medicine, Chonnam National University Hwasun Hospital, 
      Hwasun, Korea.
FAU - Park, Jinny
AU  - Park J
AD  - Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 
      Korea.
FAU - Sohn, Sang-Kyun
AU  - Sohn SK
AD  - Department of Internal Medicine, Kyungpook National University Hospital, Daegu, 
      Korea.
FAU - Moon, Joon Ho
AU  - Moon JH
AD  - Department of Internal Medicine, Kyungpook National University Hospital, Daegu, 
      Korea.
FAU - Lee, Yoo Jin
AU  - Lee YJ
AD  - Department of Internal Medicine, Kyungpook National University Hospital, Daegu, 
      Korea.
FAU - Yoon, Seonghae
AU  - Yoon S
AD  - Clinical Trials Center, Seoul National University Bundang Hospital, Seongnam, 
      Korea.
FAU - Lee, Jeong-Ok
AU  - Lee JO
AD  - Department of Internal Medicine, Seoul National University Bundang Hospital, 
      Seongnam, Korea.
FAU - Cheong, June-Won
AU  - Cheong JW
AD  - Department of Internal Medicine, Severance Hospital, Seoul, Korea.
FAU - Kim, Kyoung Ha
AU  - Kim KH
AD  - Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, 
      Korea.
FAU - Kim, Sung-Hyun
AU  - Kim SH
AD  - Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
FAU - Kim, Hoon-Gu
AU  - Kim HG
AD  - Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, 
      Korea.
FAU - Kim, Hawk
AU  - Kim H
AD  - Department of Internal Medicine, Ulsan University Hospital, Ulsan, Korea.
FAU - Nam, Seung-Hyun
AU  - Nam SH
AD  - Department of Internal Medicine, VHS Medical Center, Seoul, Korea.
FAU - Do, Young Rok
AU  - Do YR
AD  - Department of Internal Medicine, Keimyung University Dongsan Medical Center, 
      Daegu, Korea.
FAU - Park, Sang-Gon
AU  - Park SG
AD  - Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea.
FAU - Park, Seong Kyu
AU  - Park SK
AD  - Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 
      Bucheon, Korea.
FAU - Bae, Sung Hwa
AU  - Bae SH
AD  - Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, 
      Korea.
FAU - Song, Hun Ho
AU  - Song HH
AD  - Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea.
FAU - Shin, Dong-Yeop
AU  - Shin DY
AUID- ORCID: 0000-0003-1753-8846
AD  - Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea.
FAU - Oh, Doyeun
AU  - Oh D
AUID- ORCID: 0000-0002-6981-3144
AD  - Department of Internal Medicine, CHA Bundang Medical Center, Seongnam, Korea.
FAU - Kim, Min Kyoung
AU  - Kim MK
AD  - Department of Internal Medicine, Yeungnam University Medical Center, Daegu, 
      Korea.
FAU - Jung, Chul Won
AU  - Jung CW
AD  - Department of Internal Medicine, Samsung Medical Center, Seoul, Korea.
FAU - Park, Seonyang
AU  - Park S
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, Korea.
FAU - Kim, Inho
AU  - Kim I
AD  - Department of Internal Medicine, Seoul National University Hospital, Cancer 
      Research Institute, Seoul National University College of Medicine, Seoul, Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT03332511
PT  - Clinical Trial, Phase IV
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20180325
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Pyrimidines)
RN  - F41401512X (nilotinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromatography, Liquid
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Pyrimidines/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Republic of Korea
MH  - Tandem Mass Spectrometry
MH  - Treatment Outcome
PMC - PMC5943463
OTO - NOTNLM
OT  - CML
OT  - molecular response
OT  - nilotinib
OT  - prognosis
EDAT- 2018/03/27 06:00
MHDA- 2019/09/07 06:00
PMCR- 2018/03/25
CRDT- 2018/03/27 06:00
PHST- 2017/11/06 00:00 [received]
PHST- 2018/02/12 00:00 [revised]
PHST- 2018/02/26 00:00 [accepted]
PHST- 2018/03/27 06:00 [pubmed]
PHST- 2019/09/07 06:00 [medline]
PHST- 2018/03/27 06:00 [entrez]
PHST- 2018/03/25 00:00 [pmc-release]
AID - CAM41450 [pii]
AID - 10.1002/cam4.1450 [doi]
PST - ppublish
SO  - Cancer Med. 2018 May;7(5):1814-1823. doi: 10.1002/cam4.1450. Epub 2018 Mar 25.