PMID- 17264298
OWN - NLM
STAT- MEDLINE
DCOM- 20070712
LR  - 20231024
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 109
IP  - 10
DP  - 2007 May 15
TI  - Dasatinib induces significant hematologic and cytogenetic responses in patients 
      with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated 
      phase.
PG  - 4143-50
AB  - Treatment options are limited for patients with imatinib-resistant or -intolerant 
      accelerated phase chronic myeloid leukemia (CML-AP). Dasatinib is a novel, 
      potent, oral, multitargeted kinase inhibitor of BCR-ABL and SRC-family kinases 
      that showed marked efficacy in a phase 1 trial of patients with 
      imatinib-resistant CML. Results are presented for 107 patients with CML-AP with 
      imatinib-resistance or -intolerance from a phase 2, open-label study further 
      evaluating dasatinib efficacy and safety. At 8 months' minimum follow-up, 81%, 
      64%, and 39% of patients achieved overall, major (MaHR), and complete hematologic 
      responses, respectively, whereas 33% and 24% attained major and complete 
      cytogenetic remission. Of 69 patients who achieved MaHR, 7 progressed. 
      Seventy-six percent of patients are estimated to be alive and progression-free at 
      10 months. Response rates for the 60% of patients with baseline BCR-ABL mutations 
      did not differ from the total population. Dasatinib was well tolerated: most 
      nonhematologic adverse events (AEs) were mild to moderate; no imatinib-intolerant 
      patients discontinued dasatinib because of AEs. Although common (76% of patients 
      with severe neutropenia), cytopenias were manageable through dose modification. 
      In summary, dasatinib induced significant hematologic and cytogenetic responses 
      in patients with imatinib resistance or intolerance, was well tolerated, and may 
      represent a potent new therapeutic option for CML-AP. Further follow-up is 
      warranted. This trial was registered at www.clinicaltrials.gov as #CA180005.
FAU - Guilhot, Francois
AU  - Guilhot F
AD  - Clinical Research Centre, Centre Hospitalier et Universitaire La Miletrie, 
      Poitiers, France. f.guilhot@chu-poitiers.fr
FAU - Apperley, Jane
AU  - Apperley J
FAU - Kim, Dong-Wook
AU  - Kim DW
FAU - Bullorsky, Eduardo O
AU  - Bullorsky EO
FAU - Baccarani, Michele
AU  - Baccarani M
FAU - Roboz, Gail J
AU  - Roboz GJ
FAU - Amadori, Sergio
AU  - Amadori S
FAU - de Souza, Carmino A
AU  - de Souza CA
FAU - Lipton, Jeffrey H
AU  - Lipton JH
FAU - Hochhaus, Andreas
AU  - Hochhaus A
FAU - Heim, Dominik
AU  - Heim D
FAU - Larson, Richard A
AU  - Larson RA
FAU - Branford, Susan
AU  - Branford S
FAU - Muller, Martin C
AU  - Muller MC
FAU - Agarwal, Prasheen
AU  - Agarwal P
FAU - Gollerkeri, Ashwin
AU  - Gollerkeri A
FAU - Talpaz, Moshe
AU  - Talpaz M
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20070130
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazoles)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/adverse effects/therapeutic use
MH  - Benzamides
MH  - Blood Cell Count
MH  - Cytogenetic Analysis
MH  - Dasatinib
MH  - Disease Progression
MH  - Drug Resistance, Neoplasm/drug effects/genetics
MH  - Female
MH  - Fusion Proteins, bcr-abl
MH  - Humans
MH  - Imatinib Mesylate
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood/*drug 
      therapy/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Piperazines/adverse effects/*therapeutic use
MH  - Point Mutation
MH  - Protein-Tyrosine Kinases/genetics
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Thiazoles/adverse effects/*therapeutic use
MH  - Treatment Outcome
EDAT- 2007/02/01 09:00
MHDA- 2007/07/13 09:00
CRDT- 2007/02/01 09:00
PHST- 2007/02/01 09:00 [pubmed]
PHST- 2007/07/13 09:00 [medline]
PHST- 2007/02/01 09:00 [entrez]
AID - S0006-4971(20)41530-7 [pii]
AID - 10.1182/blood-2006-09-046839 [doi]
PST - ppublish
SO  - Blood. 2007 May 15;109(10):4143-50. doi: 10.1182/blood-2006-09-046839. Epub 2007 
      Jan 30.