Phase I trials of amonafide as monotherapy and in combination with cytarabine in patients with poor-risk acute myeloid leukemia

作者：Allen Steven L^*; Kolitz Jonathan E; Lundberg Ante S; Bennett John M; Capizzi Robert L; Budman Daniel R

来源：Leukemia Research, 2010, 34(4): 487-491.

DOI：10.1016/j.leukres.2009.07.038

• AML
• Phase I
• P-glycoprotein
• Pgp
• Multidrug resistance

Amonafide-L-malate ( amonafide) is a unique DNA intercalator that maintains activity in the presence of MDR mechanisms, a frequent cause of treatment-failure in secondary AML. 43 patients with relapsed/refractory or secondary AML or CML blast crisis were enrolled into two phase I dose-escalation studies investigating amonafide as monotherapy or in combination with cytarabine. 3/17 patients in the monotherapy trial and 10/26 patients in the combination trial achieved a complete remission. Between both trials responses occurred in 9/20 patients with secondary AML. Both trials demonstrated an acceptable safety profile and significant antileukemic activity in patients with poor-risk AML, especially those with secondary AML.

• 出版日期2010-4