The American journal of pathology
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Low-grade chronic cardiotoxicity as determined by myocardial biopsy specimens was induced in beagle dogs after four courses of doxorubicin hydrochloride (1.64 mg/kg, 34.0 mg/sq m) given intravenously once every 3 weeks. After this initial treatment, these dogs were separated into three groups. Two groups received six courses of mitoxantrone (0.25 mg/kg, 5 mg/sq m) commencing at 7 weeks or 19 weeks after the final doxorubicin treatment. ⋯ This study indicated that in beagle dogs four courses of doxorubicin (7 mg/kg, 136 mg/sq m cumulative dose) are the threshold dose at which non-life-threatening cardiotoxicity occurs. Residual toxic effects of doxorubicin may be erroneously interpreted as adverse findings attributable to other agents given subsequently during the susceptible period, ie, prior to stabilization of the myocardium. Mitoxantrone given after stabilization of doxorubicin-induced low-grade myocardial changes did not show additive or synergistic effects.