PMID- 17496201
OWN - NLM
STAT- MEDLINE
DCOM- 20071106
LR  - 20220321
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 7
DP  - 2007 Oct 1
TI  - Dasatinib induces rapid hematologic and cytogenetic responses in adult patients 
      with Philadelphia chromosome positive acute lymphoblastic leukemia with 
      resistance or intolerance to imatinib: interim results of a phase 2 study.
PG  - 2309-15
AB  - Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia 
      (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, 
      multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously 
      induced responses in patients with imatinib-resistant or -intolerant Ph-positive 
      ALL. We present the interim results of a phase 2 study designed to further assess 
      the efficacy, safety, and tolerability of dasatinib 140 mg in this patient 
      population (n = 36). With a minimum follow-up of 8 months, treatment with 
      dasatinib resulted in substantial hematologic and cytogenetic response rates. 
      Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom 
      remained progression-free. Complete cytogenetic responses were attained by 58% 
      (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib 
      resistance did not preclude a response to dasatinib. Dasatinib was also 
      tolerable, with 6% (2/36) of patients discontinuing therapy as a result of 
      study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile 
      neutropenia was the most frequent severe AE, but this and other cytopenias were 
      manageable with dose reduction. Dasatinib represents a safe and effective 
      treatment option and an important therapeutic advance for patients with 
      Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as 
      #CA180015.
FAU - Ottmann, Oliver
AU  - Ottmann O
AD  - Medizinische Klinik II, Johann Wolfgang Goethe Universitat, Frankfurt, Germany. 
      ottmann@em.uni-frankfurt.de
FAU - Dombret, Herve
AU  - Dombret H
FAU - Martinelli, Giovanni
AU  - Martinelli G
FAU - Simonsson, Bengt
AU  - Simonsson B
FAU - Guilhot, Francois
AU  - Guilhot F
FAU - Larson, Richard A
AU  - Larson RA
FAU - Rege-Cambrin, Giovanna
AU  - Rege-Cambrin G
FAU - Radich, Jerald
AU  - Radich J
FAU - Hochhaus, Andreas
AU  - Hochhaus A
FAU - Apanovitch, Anne Marie
AU  - Apanovitch AM
FAU - Gollerkeri, Ashwin
AU  - Gollerkeri A
FAU - Coutre, Steven
AU  - Coutre S
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070511
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazoles)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzamides
MH  - Chromosome Aberrations/*drug effects
MH  - Cytogenetics
MH  - Dasatinib
MH  - *Drug Resistance, Neoplasm
MH  - *Drug Tolerance
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Follow-Up Studies
MH  - Fusion Proteins, bcr-abl/genetics
MH  - Hematology
MH  - Humans
MH  - Imatinib Mesylate
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Piperazines/pharmacology/*therapeutic use
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/*genetics/pathology
MH  - Pyrimidines/adverse effects/pharmacology/*therapeutic use
MH  - Thiazoles/adverse effects/pharmacology/*therapeutic use
MH  - Time Factors
EDAT- 2007/05/15 09:00
MHDA- 2007/11/07 09:00
CRDT- 2007/05/15 09:00
PHST- 2007/05/15 09:00 [pubmed]
PHST- 2007/11/07 09:00 [medline]
PHST- 2007/05/15 09:00 [entrez]
AID - S0006-4971(20)60478-5 [pii]
AID - 10.1182/blood-2007-02-073528 [doi]
PST - ppublish
SO  - Blood. 2007 Oct 1;110(7):2309-15. doi: 10.1182/blood-2007-02-073528. Epub 2007 
      May 11.