Gender and Age Do Not Alter Actuarial Incidence of Cardiac Dysfunction Following Anthracycline Chemotherapy of Childhood Malignancy

Abstract 166

Anthracyclines are an important component of chemotherapy for children with malignancies, but their use is limited by the development of cardiotoxicity. Prior studies have shown that the gross incidence of late cardiotoxicity is related to cumulative dose of anthracycline, female gender and young age at time of therapy. However, because the development of cardiotoxicity may be a function of time since therapy, incidence alone may not accurately represent these relative risks. Acturial analysis of these risk factors, which would more precisely assess these risks, has not been previously published. We hypothesized that female pts and younger pts have an increased actuarial likelihood of cardiotoxicity following anthracycline therapy. The study population consisted of 344 pts treated with anthracycline-containing regimens between 1979-1997 who had at least one echocardiogram at Stanford within the past 5 yrs. Median age was 8.2 yrs (2 wks-25 yrs), median anthracycline dose was 240 mg/m² (25-575), 2/3 of patients had leukemia or lymphoma, and 188 pts (55%) were male. Cardiotoxicity was defined as a fractional shortening ≤27%. Data were analyzed using the Kaplan-Meier method. Actuarial freedom from cardiotoxicity in the entire group was 84% at 5 yrs (n=89), and 73% at 10 yrs (n=38). There were no clinically meaningful differences in cumulative anthracycline dose between males and females, or between younger and older pts. Analyzed by gender, freedom from cardiotoxicity at 5 yrs was 82% in males, and 87% in females (p=NS). At 10 yrs, freedom from cardiotoxicity was 67% in males and 78% in females (p=NS). Analyzed by age, the freedom from cardiotoxicity was 83% at 5 yrs for pts less than age 2 yrs at diagnosis, and 84% for those older than 2 yrs (p=NS), while at 10 yrs the freedom from cardiotoxicity was 69% and 72%, respectively (p=NS). CONCLUSIONS: When analyzed by actuarial methods, the incidence of cardiotoxicity following anthracycline therapy is similar in males and females, and is also not altered by age at time of therapy.