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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2763-2767. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2002-10-2998. This Article Full Text 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 Citation Map 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia Walter Fiedler, Rolf Mesters, Heike Tinnefeld, Sonja Loges, Peter Staib, Ulrich Dührsen, 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 From the Departments of Oncology/Hematology of the University Hospitals Hamburg, Münster, Cologne, Essen (GHS), Essen (Cancer Research), Frankfurt, Göttingen, AK St Georg, Hamburg (all in Germany), and Bellinzona, Switzerland; St Antonius Hospital Eschweiler, Eschweiler, Germany; Sugen Inc., South San Francisco, CA; and Pharmacia SpA., Milan, Italy. 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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