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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-10-3023. This Article Full Text (PDF) All Versions of this Article: 2002-10-3023v1 102/3/795    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 Giles, F. J Articles by Karp, J. E Search for Related Content PubMed PubMed Citation Articles by Giles, F. J Articles by Karp, J. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 4, 2002 Accepted March 10, 2003 SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes Francis J Giles*, Alison T Stopeck, Lewis R Silverman, Jeffrey E Lancet, Maureen A Cooper, Alison L Hannah, Julie M Cherrington, Anne-Marie O'Farrell, Helene A Yuen, Sharianne G Louie, Weiru Hong, Jorge E Cortes, Srdan Verstovsek, Maher Albitar, Susan M O'Brien, Hagop M Kantarjian, and Judith E Karp Department of Leukemia, The Univeristy of Texas, MD Anderson Cancer Center, Houston, TX, USA Arizona Cancer Center, Tucson, AZ, USA Mount Sinai Medical Center, New York, NY, USA University of Rochester Medical Center, Rochester, NY, USA Indianapolis Community Cancer Center, Indianapolis, IN, USA Sugen Inc., South San Francisco, CA, USA University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA * Corresponding author; email: frankgiles{at}aol.com. Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are adverse prognostic features in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). VEGF is a soluble circulating angiogenic molecule that stimulates signaling via receptor tyrosine kinases (RTK), including VEGF receptor 2 (VEGFR-2). AML blasts may express VEGFR-2, c-kit, and FLT3. SU5416 is a small molecule RTK inhibitor (RTKI) of VEGFR-2, c-kit, and both wild type and mutant FLT3. A multicenter phase II study of SU5416 was conducted in patients with refractory AML or MDS. Fifty-five patients {(33 AML, 10 (30%) primary refractory, 23 (70%) relapsed), (22 MDS, 15 (68%) relapsed)} received SU5416 145 mg/m2 twice weekly intravenously for a median of 9 weeks (range 1-55). Grade 3/4 drug-related toxicities included headaches (14%), infusion-related reactions (11%), dyspnea (14%), fatigue (7%), thrombotic episodes (7%), bone pain (5%) and gastrointestinal disturbance (4%). Eleven patients (20%) did not complete 4 weeks of therapy (10 progressive disease, 1 adverse event). Three patients (5%) achieved partial responses, 1 (2%) hematologic improvement. Single agent SU5416 had biologic and modest clinical activity in refractory AML/MDS. Overall median survival was 12 weeks in AML patients (range 4-41) and not reached in MDS patients. Most observed toxicities were attributable to drug formulation (Cremophor® or hyperosmolarity of the SU5416 preparation). Studies of other RTKI and/or other anti-angiogenic approaches, with correlative studies to examine biological effects, may be warranted in patients with AML/MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: AML beyond the boundaries of daunomycin and cytarabine Bob Löwenberg Blood 2003 102: 775. [Full Text] [PDF] This article has been cited by other articles: C. J. Hess, N. Feller, F. Denkers, A. Kelder, P. A. Merle, M. C. Heinrich, A. 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