DOXORUBICIN CARDIOTOXICITY IN AFRICAN AMERICANS

INTRODUCTION

In 1957 streptomyces peucetius was isolated from southern Italian soil. The compound 1, 4-hydroxydaunomycin was produced by a variant strain and called Adriamycin (Adria) because of the proximity of the parent strain source to Adriatic Sea. Doxorubicin hydrochloride, the generic name for Adriamycin, has a leading role in the treatment of hematological malignancies and solid tumors. It is the single most active agent for the treatment of most types of lymphoma in the “CHOP” regimen and for metastatic breast cancer in the “CAF” or “CA” regimens). These regimens ordinarily require 300-400 mg/m² of doxorubicin for CHOP, 240 mg/m² for CA, and 240-300 mg/m² for CAF.

Doxorubicin may produce early or late cardiotoxic reactions. Early effects include: a) pericarditis-myocarditis; b) significant arrhythmias especially, AV conduction block, and ventricular arrhythmia; and c) sudden onset of left ventricular dysfiinction presenting as acute cardiac failure. These early cardiac effects are idiosyncratic, apparently independent of dose and very rare. Late cardiac effects are common dose-dependent loss of left ventricular function, presenting as congestive heart failure (CHF). While the time of presentation can vary from weeks to years after receiving doxorubicin, risk correlates well with cumulative dosing, with risks 0, 5% at 400 mg/m² of body surface area and a greater-than-linear progression above this level. Although there are no reports in the literature of risk related to African race, oncologists at Howard University Hospital have long regarded African Americans as having a higher risk of doxorubicin cardiotoxicity based upon their undocumented experience. canadian discount pharmacy

Most African-American patients at Howard have received doxorubicin as a 48-hour infusion rather than the usual bolus over 30-60 minutes, a measure which should reduce the frequency of cardiotoxicity by 43%. In addition, it is well known that African Americans have a higher prevalence and earlier onset of cardiovascular diseases, hypertension, and atherosclerosis. The aim of the present study was to examine African-American race as a risk factor for cardiotoxicity from doxorubicin-based therapy.

Category: Cancer

Tags: African Americans, cardiotoxicity, doxorubicin