Document Detail


A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia.
MedLine Citation:
PMID:  12843001     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of leukemic blasts. This concept represented the rationale for the initiation of a multicenter phase 2 trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor, and fms-like tyrosine kinase-3 (FLT3) in patients with advanced AML. Entered into the study were 43 patients with refractory AML or elderly patients not judged medically fit for intensive induction chemotherapy; 42 patients received at least one dose of study drug. Treatment was generally well tolerated, with nausea, headache, and bone pain the most frequent treatment-related side effects. One patient had a morphologic remission (French-American-British [FAB] criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. There were 7 patients who achieved a partial response (reduction of blasts by at least 50% in bone marrow and peripheral blood) lasting 1 to 5 months. Patients with AML blasts expressing high levels of VEGF mRNA by quantitative polymerase chain reaction (PCR) had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the antiangiogenic effects of SU5416.
Authors:
Walter Fiedler; Rolf Mesters; Heike Tinnefeld; Sonja Loges; Peter Staib; Ulrich Duhrsen; Michael Flasshove; Oliver G Ottmann; Wolfram Jung; Franco Cavalli; Rolf Kuse; Joerg Thomalla; Hubert Serve; Anne M O'Farrell; Mark Jacobs; Nicoletta M Brega; Paul Scigalla; Dieter K Hossfeld; Wolfgang E Berdel
Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-07-03
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-06     Completed Date:  2003-11-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2763-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. fiedler@uke.uni-hamburg.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Angiogenesis Inhibitors / therapeutic use*
Bone Marrow / metabolism
Cell Separation
Enzyme Inhibitors / therapeutic use
Female
Flow Cytometry
Humans
Indoles / therapeutic use*
Leukemia, Myeloid, Acute / drug therapy*
Male
Membrane Proteins / genetics
Microcirculation
Middle Aged
Mutation
Polymerase Chain Reaction
Pyrroles / therapeutic use*
Recurrence
Remission Induction
Time Factors
Treatment Outcome
Vascular Endothelial Growth Factor A / metabolism
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Enzyme Inhibitors; 0/Indoles; 0/Membrane Proteins; 0/Pyrroles; 0/SU 5416; 0/Vascular Endothelial Growth Factor A; 0/flt3 ligand protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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