Clinical and pathological absence of cardiotoxicity after liposomal doxorubicin

To assess anthracycline-induced myocardial toxic effects pathologically, the patient consented to an endomyocardial biopsy, which showed no evidence of significant cardiotoxicity (grade 1·0 on the Billingham scale) after a total cumulative dose of 1485 mg/m2 (28 cycles) of liposomal doxorubicin (see figure). By decreasing the peak plasma concentration accompanying the 15–30 min bolus of standard 3-weekly doxorubicin, alternative regimens such as low-dose weekly and long-term infusional doxorubicin have been associated with reduced cardiotoxicity.2 Alternatively, an epimer of doxorubicin (epirubicin) has a higher cardiac cumulative dose (900 mg/m2) but similar efficacy.3 Data obtained from animals suggest that the cardiotoxicity of liposomal and polyethylene glycol (PEG)- coated liposomal doxorubicin is less than that of conventional doxorubicin at equivalent cumulative doses, because of the slow drug release (with the avoidance of high peak plasma concentrations) and less exposure to cardiac tissue.4 At present three liposomal anthracyclines are available—liposomal daunorubicin, doxorubicin, and PEGliposomal doxorubicin. Liposomal daunorubicin has been investigated in haematological malignant diseases but few trials have compared it with standard daunorubicin.3 Cardiotoxicity has been documented with higher doses of liposomal daunorubicin (600–900 mg/m2), and in one study, 750 mg/m2 was suggested as the highest acceptable cumulative dose.3 No direct prospective comparisons have been done between standard daunorubicin and the two liposomal forms of doxorubicin in terms of efficacy and toxic effects.