| A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. | |
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MedLine Citation:
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PMID: 12843001 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't Date: 2003-07-03 |
Journal Detail:
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Title: Blood Volume: 102 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2003 Oct |
Date Detail:
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Created Date: 2003-10-06 Completed Date: 2003-11-24 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2763-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. fiedler@uke.uni-hamburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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