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Blood, 1 February 2005, Vol. 105, No. 3, pp. 986-993. Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-05-1846. This Article Full Text (PDF) All Versions of this Article: 2004-05-1846v1 105/3/986    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 Hossfeld, D. K Search for Related Content PubMed PubMed Citation Articles by Fiedler, W. Articles by Hossfeld, D. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 13, 2004 Accepted September 23, 2004 A phase I study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease Walter Fiedler*, Hubert Serve, Hartmut Dohner, Michael Schwittay, Oliver G Ottmann, Anne-Marie O'Farrell, Carlo L Bello, Randy Allred, William C Manning, Julie M Cherrington, Sharianne G Louie, Weiru Hong, Nicoletta M Brega, Giorgio Massimini, Paul Scigalla, Wolfgang E Berdel, and Dieter K Hossfeld Dept. of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg, Germany Dept. of Oncology/Hematology, University Hospital Munster, Munster, Germany Dept. of Oncology/Hematology, University Hospital Ulm, Ulm, Germany Dept. of Oncology/Hematology, University Hospital Leipzig, Leipzig, Germany Dept. of Oncology/Hematology, University Hospital Frankfurt, Frankfurt, Germany Pfizer Inc., San Diego, CA, USA Pharmacia Italia S.pA., Nerviano, Italy Pharmacia Co., Bedminster, NJ, USA * Corresponding author; email: fiedler{at}uke.uni-hamburg.de. Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of Flt3, Kit, VEGF and PDGF receptors. Separate cohorts of patients received SU11248 for 4 week cycles followed by either a 2 or 1 week rest period. At the starting dose level of 50 mg (n= 13) no dose limiting toxicities were observed. The most frequent grade 2 toxicities were edema, fatigue and oral ulcerations. Two fatal bleedings possibly related to the disease, one from a concomitant lung cancer and one cerebral bleeding were observed. At the 75 mg dose level (n=2), one case each of grade 4 fatigue, hypertension and cardiac failure was observed and this dose level abandoned. All patients with FLT3 mutations (n=4) had morphological or partial responses compared to 2 out of 10 evaluable patients with wildtype FLT3. Responses, although longer in patients with mutated FLT3, were of short duration. Reductions of cellularity and numbers of Ki-67, phospho-Kit, phospho-KDR, phospho-STAT5 and phospho-Akt positive cells were detected in bone marrow histology analysis. In summary, monotherapy with SU11248 induced partial remissions of short duration in AML patients. Further evaluation of this compound, for example in combination with chemotherapy is warranted. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. L. Bello, M. Mulay, X. Huang, S. Patyna, M. Dinolfo, S. Levine, A. Van Vugt, M. Toh, C. Baum, and L. Rosen Electrocardiographic Characterization of the QTc Interval in Patients with Advanced Solid Tumors: Pharmacokinetic- Pharmacodynamic Evaluation of Sunitinib Clin. Cancer Res., November 15, 2009; 15(22): 7045 - 7052. [Abstract] [Full Text] [PDF] P. P. Zarrinkar, R. N. Gunawardane, M. D. Cramer, M. F. Gardner, D. Brigham, B. Belli, M. W. Karaman, K. W. Pratz, G. Pallares, Q. Chao, et al. 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