Amonafide: A future in treatment of resistant and secondary acute myeloid leukemia?

Ciara L. Freeman, Ronan Swords, Francis J. Giles

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17-26
Number of pages10
JournalExpert Review of Hematology
Volume5
Issue number1
DOIs
StatePublished - Feb 1 2012

Keywords

  • AML
  • amonafide (l-malate)
  • cytarabine (ARA-C)
  • MDR proteins
  • multidrug resistance
  • N-acetyltransferase 2 (NAT2)
  • naphthalimides
  • P-glycoprotein
  • secondary AML/treatment-related AML (sAML/tAML)
  • topoisomerase II inhibitor

ASJC Scopus subject areas

  • Hematology

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