Researchers from several U.S. Medical Centers have reported that the combination of Quinamed® (amonafide, benzisoquinolinedione, nafidimide) and ara-C is active in the treatment of patients with secondary acute myeloid leukemia (sAML). The details of this Phase II study were presented at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, May 30-June 2.1
The dihydrochloride salt of amonafide is an imide derivative of naphthalic acid. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in protein-associated strand breaks and impaired DNA and RNA synthesis. This agent is a unique ATP-independent Topo II inhibitor, which has been evaluated in conjunction with ara-c for the treatment of patients with sAML with promising results.
The current study is a follow-up of data presented at ASCO 2007.2 This study has now enrolled 80 patients with poor-risk sAML; data were presented on the outcomes of 40 patients. The median age of this group was 63 years. The complete response (CR) rate was 57% for patients who had prior myelodysplastic syndrome, 43% for those with treatment-related AML, and 40% for those with unfavorable cytogenetics. The median duration of CR was 28 weeks. Mortality in the first month was 17%. Eight of 16 patients remain in continuous CR. These authors concluded that this drug combination was promising, especially in patients with over-expression of P-glycoprotein.
Comments: Quinamed may be a very important addition to therapies available for poor-risk AML.
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Reference:
1 Rizzieri DA, Erba M, O’Donnell M, et al. Amonafide + ara-C in secondary acute myeloid leukemia (sAML): Consistent efficacy in poor risk populations. Journal of Clinical Oncology. 2008;26:abstract 7027.
2 Erba HP, Rizzieri DA, O’Donnell MR, et al. Amonafide and ara-C treatment for secondary acute myeloid leukemia (sAML). Journal of Clinical Oncology. 2007;25: abstract 7065.
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