PMID- 28699641
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20231112
IS  - 1365-2141 (Electronic)
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 179
IP  - 2
DP  - 2017 Oct
TI  - Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in 
      chronic phase: final results from ENESTxtnd.
PG  - 219-228
LID - 10.1111/bjh.14829 [doi]
AB  - The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending 
      Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of 
      molecular response to nilotinib in patients with newly diagnosed chronic myeloid 
      leukaemia in chronic phase and the impact of novel dose-optimization strategies 
      on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation 
      (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment 
      failure as well as dose re-escalation for patients with nilotinib dose reductions 
      due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70.8% (95% 
      confidence interval, 66.2-75.1%) achieved major molecular response 
      (BCR-ABL1 </= 0.1% on the International Scale) by 12 months (primary endpoint). By 
      24 months, 81.0% of patients achieved major molecular response, including 63.6% 
      (56 of 88) of those with dose escalations for lack of efficacy and 74.3% (55 of 
      74) of those with dose reductions due to adverse events (including 43 of 54 
      patients with successful re-escalation). The safety profile of nilotinib was 
      consistent with prior studies. The most common non-haematological adverse events 
      were headache, rash, and nausea; cardiovascular events were reported in 4.5% of 
      patients (grade 3/4, 3.1%). The study was registered at clinicaltrials.gov 
      (NCT01254188).
CI  - (c) 2017 The Authors. British Journal of Haematology published by John Wiley & Sons 
      Ltd.
FAU - Hughes, Timothy P
AU  - Hughes TP
AUID- ORCID: 0000-0002-0910-3730
AD  - South Australian Health and Medical Research Institute (SAHMRI), University of 
      Adelaide, SA Pathology, Adelaide, SA, Australia.
FAU - Munhoz, Eduardo
AU  - Munhoz E
AD  - Hospital Erasto Gaertner - Liga Paranaense Combate ao Cancer, Curitiba, Brazil.
FAU - Aurelio Salvino, Marco
AU  - Aurelio Salvino M
AD  - Hospital Sao Rafael-Monte Tabor & Hospital Universitario Professor Edgard 
      Santos-Universidade Federal da Bahia, Salvador, Brazil.
FAU - Ong, Tee Chuan
AU  - Ong TC
AD  - Hospital Ampang, Selangor, Malaysia.
FAU - Elhaddad, Alaa
AU  - Elhaddad A
AD  - National Cancer Institute, Cairo University, Cairo, Egypt.
FAU - Shortt, Jake
AU  - Shortt J
AD  - School of Clinical Sciences at Monash Health, Monash University, Clayton, Vic., 
      Australia.
FAU - Quach, Hang
AU  - Quach H
AD  - St Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
FAU - Pavlovsky, Carolina
AU  - Pavlovsky C
AD  - FUNDALEU, Hospitalization and Clinical Research Centre, Buenos Aires, Argentina.
FAU - Louw, Vernon J
AU  - Louw VJ
AD  - University of the Free State, Bloemfontein, South Africa.
FAU - Shih, Lee-Yung
AU  - Shih LY
AD  - Chang Gung Memorial Hospital-Linkou, Chang Gung University, Taoyuan City, Taiwan.
FAU - Turkina, Anna G
AU  - Turkina AG
AD  - FGB Haematology Research Centre Health Ministry Research Facility, Moscow, 
      Russia.
FAU - Meillon, Luis
AU  - Meillon L
AD  - Hospital de Especialidades, CMN Siglo XXI, Mexico City, Mexico.
FAU - Jin, Yu
AU  - Jin Y
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Acharya, Sandip
AU  - Acharya S
AD  - Novartis Healthcare Pvt. Ltd., Hyderabad, India.
FAU - Dalal, Darshan
AU  - Dalal D
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Lipton, Jeffrey H
AU  - Lipton JH
AD  - Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
LA  - eng
SI  - ClinicalTrials.gov/NCT01254188
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170712
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Pyrimidines)
RN  - F41401512X (nilotinib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cardiovascular Diseases/chemically induced/epidemiology
MH  - Female
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/*drug 
      therapy/epidemiology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Pyrimidines/*administration & dosage/adverse effects
PMC - PMC5655928
OTO - NOTNLM
OT  - chronic myeloid leukaemia
OT  - dose optimization
OT  - molecular response
OT  - nilotinib
OT  - tyrosine kinase inhibitor
EDAT- 2017/07/13 06:00
MHDA- 2017/10/20 06:00
PMCR- 2017/10/25
CRDT- 2017/07/13 06:00
PHST- 2017/02/21 00:00 [received]
PHST- 2017/05/29 00:00 [accepted]
PHST- 2017/07/13 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
PHST- 2017/07/13 06:00 [entrez]
PHST- 2017/10/25 00:00 [pmc-release]
AID - BJH14829 [pii]
AID - 10.1111/bjh.14829 [doi]
PST - ppublish
SO  - Br J Haematol. 2017 Oct;179(2):219-228. doi: 10.1111/bjh.14829. Epub 2017 Jul 12.