Researchers affiliated with the European Organization for Research on Treatment of Cancer (EORTC) have reported that patients with non-Hodgkin lymphoma (NHL) who receive six cycles of doxorubicin have an increased risk of cardiovascular disease, especially of chronic heart failure. The details of this study were published in the April 1, 2006 issue of Blood.[1]

Delayed cardiac toxicity is frequent in patients receiving high-doses of anthracyclines for the treatment of NHL. The incidence of congestive heart failure in patients receiving more than 550 mg/m2 of doxorubicin is estimated to be 30%. Approximately 4% of such patients developed congestive heart failure after receiving cumulative doses of 500-550 mg/m2. In response, most clinicians try to limit exposure to anthracyclines to cumulative doses of less than 550 mg/m2 of doxorubicin.

A recent French study evaluated 141 relatively young patients (median of 47 years) with lymphoma who had received more than 250 mg/m2 of doxorubicin. Only 7% had received more than 400 mg/m2 of doxorubicin; the highest cumulative dose was 550 mg/m2. They found only one patient with clinical congestive heart failure. However, 27.7% had sub-clinical cardiomyopathy as measured by echocardiograms. In multivariate analyses, sub-clinical cardiomyopathy was associated with higher doses of anthracyclines, older age, radiotherapy, and obesity.

The current study used standardized morbidity incidences from patients without NHL to compare with incidences observed in 476 patients with NHL who had received six cycles of doxorubicin. The median follow-up was 8.4 years. They found a 5-fold increase in the incidence of chronic heart failure and a 1.5-fold increase in stroke. There was, however, no increase in coronary artery disease, myocardial infarction, or angina pectoris. Risk of stroke was increased in patients receiving radiotherapy. Factors that increased the risk of cardiovascular events included preexisting hypertension, young age at diagnosis, and salvage therapy. These authors suggested that these data emphasize the need for long-term follow-up of patients with NHL who have received anthracyclines.

Comments: The obvious question, which can only be asked with long-term studies, is whether or not the newer pegylated and lysosomal anthracyclines, such as Doxil®, will have an impact on late cardiomyopathy. Given the wide variety of agents available for the treatment of NHL, it may be possible to lower the cumulative dose-limit of doxorubicin to 300 or 400 mg/m2.

Related News: Subclinical Cardiomyopathy is Frequent after Usual Dosage of Anthracyclines for Treatment of Lymphoma (5/17/2004)

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