A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia.
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A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia. / 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.
In: BLOOD, Vol. 102, No. 8, 8, 2003, p. 2763-2767.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia.
AU - Fiedler, Walter
AU - Mesters, Rolf
AU - Tinnefeld, Heike
AU - Loges, Sonja
AU - Staib, Peter
AU - Duhrsen, Ulrich
AU - Flasshove, Michael
AU - Ottmann, Oliver G
AU - Jung, Wolfram
AU - Cavalli, Franco
AU - Kuse, Rolf
AU - Thomalla, Joerg
AU - Serve, Hubert
AU - O'Farrell, Anne M
AU - Jacobs, Mark
AU - Brega, Nicoletta M
AU - Scigalla, Paul
AU - Hossfeld, Dieter K
AU - Berdel, Wolfgang E
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 102
SP - 2763
EP - 2767
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 8
M1 - 8
ER -