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mechanisms which are involved in the cardiotoxicity and antineoplastic activity of
adriamycin are still not clearly defined.
I.g.l.Dose and schedule optimization: Since the proposed dose limitation of 550 md^'
of body surface area, several different administration regimes were examined. The study
on adult cancer patients treated with prolonged adriamycin infusions over; 6,48 and 96
hours, has reported that this prolonged treatment protocol resulted in less cardiotoxic
side-effects when compared to the bolus administration regimes (Bielack et al. 1989;
Legha et al. 1982). However, the replacement of the bolus administration with slow
infusion was not found beneficial in pediatric patients (Lipshultz et al.2002). The most
severe complication of prolonged administration of adriamycin is a development of the
extensive damage to peripheral blood mononuclear cells (Minotti et aL.2004).
I.g.2.Search for less toxic analogues: Structural analogues of adriamycin, such as
mitoxantrone, idarubicine and epirubicine, have exhibited reduced cardiotoxic sideeffects,
however, this was accompanied by the reduction in antitumor efficiency
(Henderson et al. 1989). The new approach to this problem is to develop the antracycline
analogues that will specif,rcally target tumor tissue without exposing healthy tissue to the
potential toxic levels of the anticancer drug (Drummond et al. 1999). Encapsulation of
anticancer drugs in to liposome carrier was found to provide better targeting of tumor
cells and at the same time provided the reduction in the occurrence of side effects of
antineoplastic treatment. The usage of liposomal preparations of antracyclines has
already shown some promise (Drummond et al.1999).
I.g.3.Calcium-channel blockers: The usage of calcium channel blockers in
prevention of adriamycin-induced cardiotoxicity is based on the concept that
the
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