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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 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 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 Hossfeld, D. K. Search for Related Content PubMed PubMed Citation Articles by Fiedler, W. Articles by Hossfeld, D. K. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS A phase 1 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 Döhner, 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 From the Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Oncology/Hematology, University Hospital Münster, Germany; Department of Oncology/Hematology, University Hospital Ulm, Germany; Department of Oncology/Hematology, University Hospital Leipzig, Germany; Department of Oncology/Hematology, University Hospital Frankfurt, Germany; Pfizer, La Jolla, CA; Pfizer, San Diego, CA; Pharmacia Italia, Nerviano, Italy, and Pharmacia, Bedminster, NJ. Fifteen patients with refractory AML were treated in a phase 1 study with SU11248, an oral kinase inhibitor of fms-like tyrosine kinase 3 (Flt3), Kit, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) receptors. Separate cohorts of patients received SU11248 for 4-week cycles followed by either a 2- or a 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 was abandoned. All patients with FLT3 mutations (n = 4) had morphologic or partial responses compared with 2 of 10 evaluable patients with wild-type FLT3. Responses, although longer in patients with mutated FLT3, were of short duration. Reductions of cellularity and numbers of Ki-67+, phospho-Kit+, phospho–kinase domain–containing receptor–positive (phospho-KDR+), phospho–signal transducer and activator of transcription 5–positive (phospho-STAT5+), and phospho-Akt+ cells were detected in bone marrow histology analysis. In summary, monotherapy with SU11248 induced partial remissions of short duration in acute myeloid leukemia (AML) patients. 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