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finding, clinical studies have shown that replacing DOX with EPI does not eliminate the risk of chronic cardiotoxicity. IDA, an analog of DNR obtained by removal of the methoxy group, has a broader spectrum of activity. This is probably related to its increased lipophilicity, which facilitates the cellular uptake and contributes to stabilize the ternary complex that forms the drug with DNA and topoisomerase II (see Chapter 7). The last effect is important, since a major mechanism of anthracycline activity depends on the formation of this complex. However, the cardiac safety of IDA has not been clearly established.

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