myeloid leukemia A phase II clinical study of SU5416 in patients with refractory acute

Abstract Neoangiogenesis has been shown to play an important role in the pathogenesis of 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 multi-center phase II trial of SU5416, a small molecule inhibitor of phosphorylation of VEGF receptors 1 and 2, c-kit, the SCF receptor and FLT3 in patients with advanced AML. Forty-three patients with refractory AML or elderly patients not judged medically fit enough for intensive induction chemotherapy were entered into the study. Forty-two patients received at least one dose of study drug. Treatment was generally well tolerated with nausea, headache and bone pain being the most frequent treatment related side effects. One patient had a morphological remission (FAB criteria of complete response without normalization of blood neutrophil and platelet counts) lasting for 2 months. Seven patients 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 m-RNA by quantitative PCR had a significantly higher response rate and reduction of bone marrow microvessel density than patients with low VEGF expression consistent with the anti-angiogenic effects of SU5416.From bloodjournal.hematologylibrary.org by guest on May 29, 2013. For personal use only.