A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia |
| |
Authors: | Fiedler Walter Mesters Rolf Tinnefeld Heike Loges Sonja Staib Peter Duhrsen Ulrich Flasshove Michael Ottmann Oliver G Jung Wolfram Cavalli Franco Kuse Rolf Thomalla Joerg Serve Hubert O'Farrell Anne M Jacobs Mark Brega Nicoletta M Scigalla Paul Hossfeld Dieter K Berdel Wolfgang E |
| |
Affiliation: | Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. fiedler@uke.uni-hamburg.de |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
| 点击此处可从《Blood》浏览原始摘要信息 |
|
点击此处可从《Blood》下载全文 |
|