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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-10-2998. This Article Full Text (PDF) All Versions of this Article: 2002-10-2998v1 102/8/2763    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fiedler, W. Articles by Berdel, W. E Search for Related Content PubMed PubMed Citation Articles by Fiedler, W. Articles by Berdel, W. E Social Bookmarking                   What's this? Submitted October 2, 2002 Accepted June 22, 2003 A phase II clinical study of SU5416 in patients with refractory acute myeloid leukemia 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, and Wolfgang E Berdel Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany Department of Oncology/Hematology, University Hospital Muenster, Muenster, Germany Department of Oncology/Hematology, University Hospital Cologne, Cologne, Germany Department of Hematology, University Hospital Essen (GHS), Essen, Germany Department of Oncology/Hematology, University Hospital Essen (Cancer Research), Essen, Germany Department of Oncology/Hematology, University Hospital Frankfurt, Frankfurt, Germany Department of Oncology/Hematology, University Hospital Goettingen, Goettingen, Germany Department of Oncology/Hematology, University Hospital Bellinzona, Bellinzona, Switzerland Department of Hematology, AK St. Georg, Hamburg, Germany Department of Hematology, St. Antonius Hospital, Eschweiler, Germany Sugen Inc., South San Francisco, CA, USA Pharmacia S.p.A., Milan, Italy * Corresponding author; email: fiedler{at}uke.uni-hamburg.de. Neoangiogenesis has been shown to play an important role in the pathogenesis of 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 multi-center phase II trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor and FLT3 in patients with advanced AML. Forty-three patients with refractory AML or elderly patients not judged medically fit enough for intensive induction chemotherapy were entered into the study. Forty-two patients received at least one dose of study drug. Treatment was generally well tolerated with nausea, headache and bone pain being the most frequent treatment related side effects. One patient had a morphological remission (FAB criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. Seven patients 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 m-RNA by quantitative PCR had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the anti-angiogenic effects of SU5416. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. A. Powell, D. Thomas, E. F. Barry, C. H. Kok, B. J. McClure, A. Tsykin, L. B. To, A. Brown, I. D. Lewis, K. Herbert, et al. 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