AS1413 (amonafide malate, formerly XanafideŽ)
AS1413 is a DNA intercalator that induces apoptotic signalling by blocking TopoII binding to DNA. Unlike classical TopoII inhibitors, which induce apoptosis by causing extensive DNA damage, AS1413 causes apoptosis by chromatin disorganisation. A further distinctive feature of AS1413 is its ability to evade PgP and related transporters responsible for multi-drug resistance. AS1413 is currently in phase III development in secondary AML.
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Secondary AML (acute myeloid leukaemia)
AML is divided into two major categories, de-novo and secondary. AML is classified as secondary AML if it occurs as a result of a prior haematological disease or treatment with chemotherapy or radiation therapy or a combination of the two causes. In a phase II trial, treatment with AS1413 plus cytarabine resulted in a complete response rate of 38.6%, with an additional 3.4% showing Cri (complete response without recovery of blood cell count). This compares with CR rates of roughly 25% seen with standard AML treatment. AS1413 is now in a phase III registration trial under Special Protocol Assessment. The phase III trial compares AS1413 plus cytarabine with daunorubicin plus cytarabine in 350 patients and began patient dosing in October 2007.



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