DOXORUBICIN CARDIOTOXICITY IN AFRICAN AMERICANS

DISCUSSION

Late cardiotoxic effects of doxorubicin are an increasing problem for large numbers of patients who survive cancer. This cardiotoxicity is often progressive and disabling. In a retrospective study of 399 patient records, CHF and cardiomyopathy were found to be dose-dependent, and the incidence of these complications increased considerably when the cumulative dose of the drug exceeded 400 mg per square meter of body-surface area. Several risk factors have been recognized for doxorubicin-induced cardiomyopathy: age >70 years, combination chemotherapy, previous or concomitant mediastinal radiotherapy, underlying cardiac disease, hypertension, and liver disease. To our knowledge, race has not previously been reported as a significant risk factor of doxorubicin cardiotoxicity. It is, therefore, important that we identified a nearly three-fold greater rate of this cardiotoxicity in our population of African-American patients in comparison with earlier studies with unknown racial distribution.

While African race is a risk factor for hypertensive and atherosclerotic, this risk would be approximately 1.25- to 1.3-fold at the median age of our study population (46 years). Therefore, it is unlikely that most of this increased risk was due to concurrent cardiovascular disease.

The major limitations of this study are its relatively small size and the lack of concurrent patients treated at the same institution who were not African. We plan to embark on retrospective and prospective surveillance of doxorubicin toxicity within institutions with multiracial patient populations.

It is particularly disturbing that such a high risk of cardiotoxicity was found among a cancer practice in which there has been a strong tradition to protect African-American patients from doxorubicin cardiotoxicity by utilizing long infusion times (two to four days) or immediate pretreatment with dexra-zoxane. Our study serves to emphasize the limitations of most prior studies which largely recruited Caucasian patients. We suspect that the true risk of this toxicity among African Americans might be 40% greater than estimated from this study, assuming that longer infusions or use of dexrazoxane have a similar protective effect among African Americans as among Caucasians. A direct test of this hypothesis is urgently needed.
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CONCLUSION

We have shown for the first time that African Americans appear to suffer cardiotoxicity from doxorubicin three times more frequently than the previously mentioned study population. This observation is particularly disturbing since most of our patients received protective measures thought to reduce this cardiotoxicity by 40-50% in contrast to those of the non-African control group. A larger study in a multiracial setting is needed to clarify this observation. This data, because of the numbers involved and lack of head-to-head comparison cannot be definitive.

Category: Cancer

Tags: African Americans, cardiotoxicity, doxorubicin