Doxorubicin cardiotoxicity in African Americans

The African-American race was examined as a risk factor for cardiotoxicity from doxorubicin-based therapy for cancer.

Retrospective survey of the Howard University Hospital cancer registry during 1997-2001 identified 100 evaluable patients out of 120 African Americans who underwent doxorubicin-based combination chemotherapy (65% women, 35% men, median age 46 years, range 32-84 years). The fraction of patients who developed post-treatment cardiotoxicity, defined as congestive heart failure or a left-ventricular ejection fraction less than 45%, was compared with that from a retrospective study of 399 patients of unknown age and racial distribution. Cases were stratified by cumulative dose of doxorubicin. Statistical significance of the difference in incidence of cardiotoxicity was tested by chi-square analysis.

Patients received multiple doses of doxorubicin (range 264 to 580 mg/m2 with median of 374) with the final echocardiographic assessment at a median of 1.3 years. Howard oncologists frequently used a 48-hour infusion rather than the conventional rapid bolus to reduce the cardiotoxicity of doxorubicin. The fraction with cardiotoxicity in our study versus Lefrak's review at four ranges of doxorubicin was 25% versus 18% at 551-600 mg/m2, 10% versus 4% at 501-550 mg/m2, 4% versus 1% at 451-500 mg/m2, and 0% versus <1% at <450 mg/m2. Seventy-two percent of the patients having depressed ejection fraction and/or heart failure were women. African Americans had a higher rate of cardiotoxicity after doxorubicin (7/100 cases) than that of Lefrak's (10/399) study population and were statistically significant at p<0.027 with an odds ratio of 2.93.

We have shown for the first time that African Americans at our institution appear to suffer cardiotoxicity from doxorubicin three times more frequently than the previously noted study population. To better clarify this observation, a larger study in a multiracial setting is needed.