PMID- 21732337
OWN - NLM
STAT- MEDLINE
DCOM- 20120213
LR  - 20220321
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 1
DP  - 2012 Jan 1
TI  - Expanding Nilotinib Access in Clinical Trials (ENACT): an open-label, multicenter 
      study of oral nilotinib in adult patients with imatinib-resistant or 
      imatinib-intolerant Philadelphia chromosome-positive chronic myeloid leukemia in 
      the chronic phase.
PG  - 118-26
LID - 10.1002/cncr.26249 [doi]
AB  - BACKGROUND: Nilotinib is a selective, potent BCR-ABL inhibitor. Previous studies 
      demonstrated the efficacy and safety of nilotinib in Philadelphia 
      chromosome-positive chronic myeloid leukemia patients in chronic phase (CML-CP) 
      or accelerated phase who failed prior imatinib. METHODS: This expanded access 
      trial further characterized the safety of nilotinib 400 mg twice daily in 
      patients with CML-CP (N = 1422). RESULTS: In this large, heavily pretreated 
      population, nilotinib demonstrated significant efficacy, with complete 
      hematologic response and complete cytogenetic response achieved in 43% and 34% of 
      patients, respectively. Responses were rapid, mostly occurring within 6 months, 
      and were higher in patients with suboptimal response to imatinib, with 75% and 
      50% achieving major cytogenetic response and complete cytogenetic response, 
      respectively. At 18 months, the progression-free survival rate was 80%. Most 
      patients achieved planned dosing of 400 mg twice daily and maintained the dose 
      >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and 
      included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4 
      thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed 
      by dose reduction or brief interruption. Grade 3 or 4 elevations in serum 
      bilirubin and lipase occurred in 4% and 7% of patients, respectively. The 
      incidence of newly occurring AEs decreased over time. Of patients who experienced 
      a dose reduction because of AEs and attempted a re-escalation, 87% successfully 
      achieved re-escalation to the full dose. CONCLUSIONS: This large study confirms 
      that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently 
      and were manageable through transient dose interruptions.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Nicolini, Franck E
AU  - Nicolini FE
AD  - Department of Hematology, Edouard Herriot Hospital, Lyon, France. 
      franck-emmanuel.nicolini@chu-lyon.fr
FAU - Turkina, Anna
AU  - Turkina A
FAU - Shen, Zhi-Xiang
AU  - Shen ZX
FAU - Gallagher, Neil
AU  - Gallagher N
FAU - Jootar, Saengsuree
AU  - Jootar S
FAU - Powell, Bayard L
AU  - Powell BL
FAU - De Souza, Carmino
AU  - De Souza C
FAU - Zheng, Ming
AU  - Zheng M
FAU - Szczudlo, Tomasz
AU  - Szczudlo T
FAU - le Coutre, Philipp
AU  - le Coutre P
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20110705
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - F41401512X (nilotinib)
SB  - IM
CIN - Cancer. 2012 Oct 15;118(20):5180-1; author reply 5181-2. PMID: 22535585
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Benzamides
MH  - Compassionate Use Trials
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Fusion Proteins, bcr-abl/*antagonists & inhibitors
MH  - Humans
MH  - Imatinib Mesylate
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Piperazines/*pharmacology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Pyrimidines/administration & dosage/adverse effects/*pharmacology/*therapeutic 
      use
MH  - Treatment Outcome
EDAT- 2011/07/07 06:00
MHDA- 2012/02/14 06:00
CRDT- 2011/07/07 06:00
PHST- 2011/01/07 00:00 [received]
PHST- 2011/03/31 00:00 [revised]
PHST- 2011/04/13 00:00 [accepted]
PHST- 2011/07/07 06:00 [entrez]
PHST- 2011/07/07 06:00 [pubmed]
PHST- 2012/02/14 06:00 [medline]
AID - 10.1002/cncr.26249 [doi]
PST - ppublish
SO  - Cancer. 2012 Jan 1;118(1):118-26. doi: 10.1002/cncr.26249. Epub 2011 Jul 5.