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Although a number of studies have reported the protective effects of nonenzymatic
antioxidants against adriamycin produced cardiotoxicity, the exact mechanism of this
protection still remains to be fully examined. This is more complicated by the fact that
vitamin doses necessary for adequate protection fairly exceed the recommended doses,
which increases the risk for the development hypervitaminosis.
Iron Chelation: The role of iron in the pathogenesis of adriamycin-induced free
radical cell damage has been widely accepted. The usage of several iron chelators was
shown to be beneficial in the prevention of cardiotoxic effects of adriamycin. These
chelators such as dexrazoxane (ICRF-187) arc currently used in clinical practice as
effective tools against the development of adriamycin-induced heart faiiure. The usage of
dexrazoxane was shown not to interfere with the distribution, metabolism, excretion and
antitumor effects of adriamycin. The same drug was found to offer significant protection
against the general toxic effects of adriamycin by lowering the occurrence of both acute
and chronic cardiotoxic effects of adriamycin (Minotti et al. 1999). Recent studies have
indicated that dexrazoxane may also posses anticancer properties and this is achieved by
its binding and inactivating of topoisomerase II (Jensen et al. 2000). Weather this effect
will interfere against adriamycin's antineoplastic properties is currently been examined.
The current guidelines for clinical usage of dexrazoxane by the American Society of
Clinical Oncology, Chemotherapy and Radiotherapy recommends the usage of this drug
in patients who have already received adriamycin in a cumulative doses above 300
mglmz as a part of their treatment against metastatic breast cancer or some other
malignancies (Schuchter et al. 2002).
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