title: Amonafide: a future in treatment of resistant and secondary acute myeloid leukemia?
abstract: Development of the novel topoisomerase II inhibitor, amonafide, began almost 40 years ago. The drug was selected for further investigation owing to evidence of marked antineoplastic efficacy in preclinical models of cancer. When its usefulness in the treatment of various solid malignancies proved limited, focus was shifted to establishing its use as an antileukemic agent, specifically against secondary and treatment-associated acute myeloid leukemia (AML). While Phase I and II studies gave rise to hopes that amonafide might hold the key to treating older patients, including those with multidrug resistant, cytogenetically unfavorable secondary and treatment-associated AML, when used in combination with cytarabine, it failed to demonstrate a survival advantage over standard-of-care therapy in randomized studies. This article will outline the development of amonafide from the laboratory to the bedside and discuss the potential place that this agent has in the current management of AML.
authors.affiliation: Mayo Clinic Phoenix Campus, Department of Hematology & Oncology, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA. freemanciara@yahoo.co.uk
authors.forename: Ciara L
authors.initials: CL
authors.lastname: Freeman
authors.forename: Ronan
authors.initials: R
authors.lastname: Swords
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000225:Adenine; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D053644:Naphthalimides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D063065:Organophosphonates; D059005:Topoisomerase II Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D053644:Naphthalimides; D063065:Organophosphonates; D059005:Topoisomerase II Inhibitors; C037020:amonafide; D000225:Adenine