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Pegylated and Nonpegylated Liposomal Doxorubicin Reduce Risk of Cardiotoxicity

Liposomal doxorubicin formulations decrease the risk of cardiotoxicity seen with conventional doxorubicin without compromising antitumour activity, even when administered at high cumulative doses.

The strongest evidence of increased cardiac safety with new liposomal anthracycline formulation is derived from prospective and retrospective trials of pegylated liposomal doxorubicin, report Maria Theodoulou, MD, Study Chair, and Clifford A. Hudis, Chief, Breast Cancer Medicine Service Memorial Sloane Kettering Center, New York, United States.

Patients treated with conventional doxorubicin present with rhythm disturbances, abnormal electrocardiographic changes, and acute but reversible reductions in left ventricular ejection fraction. Congestive cardiomyopathy, a chronic complication of conventional doxorubicin treatment, correlates with peak plasma doxorubicin concentrations as well as with the lifetime cumulative dose administered. The usual recommended lifetime cumulative dose of conventional doxorubicin is now limited to 450-550 mg/mē and could be as low as 300 mg/mē, according to a more recent study.

Patients who have received high cumulative doses of doxorubicin, elderly patients and very young children, patients with a history of cardiac disease or previous cancer therapies, are all at increased risk for the development of cardiac events associated with conventional doxorubicin.

Data from several studies suggest that nonpegylated doxorubicin may be less cardiotoxic than conventional doxorubicin. The median cumulative doxorubicin dose at the onset of cardiomyopathy was significantly higher with nonpegylated liposomal doxorubicin (785 mg/mē compared with 570 mg/mē for conventional doxorubicin; P = .0001).

Significantly fewer patients treated with nonpegylated liposomal doxorubicin developed congestive heart failure than those who received conventional doxorubicin (2% versus 8%; P = .0001). Cardiotoxicity was observed in 6% of patients treated with nonpegylated liposomal doxorubicin compared with 21% of patients who received conventional doxorubicin (P = .0001).

In pegylated liposomal doxorubicin, a polyethylene glycol layer surrounds the doxorubicin-containing liposome, which protects the liposome from detection by the mononuclear phagocyte system.

Nonpegylated liposomal doxorubicin demonstrates greater cardiac safety compared with conventional doxorubicin even in patients who have a history of conventional adjuvant anthracycline treatment, the authors note.

"Liposomal anthracyclines represent an exciting development in cancer chemotherapy," they conclude.

Cancer 2004 May 15;100(10):2052-63

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