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Author Allen, S.L.; Lundberg, A.S. file  url
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  Title Amonafide: a potential role in treating acute myeloid leukemia Type Journal Article
  Year 2011 Publication Expert Opinion on Investigational Drugs Abbreviated Journal (up) Expert Opin Investig Drugs  
  Volume 20 Issue 7 Pages 995-1003  
  Keywords Animals; Antineoplastic Agents--pharmacokinetics, therapeutic use; Clinical Trials as Topic--methods; DNA Topoisomerases, Type II--metabolism; Drug Resistance, Neoplasm; Enzyme Inhibitors--pharmacokinetics, therapeutic use; Humans; Leukemia, Myeloid, Acute--drug therapy, enzymology, mortality; Naphthalimides--pharmacokinetics, therapeutic use; Survival Rate--trends; Treatment Outcome  
  Abstract INTRODUCTION: Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA. Amonafide retains cytotoxic activity even in the presence of P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR), a major contributor to clinical treatment failure. AREAS COVERED: In vitro, Pgp-mediated transport (efflux) of amonafide from myeloblasts obtained from patients with secondary acute myeloid leukemia (sAML) was significantly less than efflux of daunorubicin. Amonafide has shown efficacy in patients with sAML, as well as in patients with poor prognostic characteristics such as older age and unfavorable cytogenetics, all associated with MDR. Improved antileukemic activity is observed when amonafide is given together with cytarabine, rather than as monotherapy, with a complete remission rate of approximately 40% in a recent Phase II trial in sAML. The efficacy of amonafide was maintained among poor-risk subsets of patients, including older patients and patients who had previous myelodysplastic syndrome or previous leukemogenic therapy. The safety profile was acceptable and manageable. EXPERT OPINION: Amonafide plus cytarabine may have clinical utility in patients with sAML and in other poor-risk subgroups of acute myeloid leukemia (AML). Ongoing trials will help define the role for amonafide in the treatment of poor-risk AML.  
  Call Number Serial 199  
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