Journal of Clinical Oncology, Vol 15, 1544-1552, Copyright © 1997 by American Society of Clinical Oncology
Clinical cardiotoxicity following anthracycline treatment for childhood cancer: the Pediatric Oncology Group experience
JP Krischer, S Epstein, DD Cuthbertson, AM Goorin, ML Epstein and SE Lipshultz
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. jpKrischer@moffitt.usf.edu
PURPOSE: To determine the incidence of clinical cardiotoxicity from
anthracycline chemotherapy in children with cancer and to identify
associated risk factors. PATIENTS AND METHODS: The study population
consisted of 6,493 children with cancer who had received anthracycline
chemotherapy on Pediatric Oncology Group (POG) protocols from 1974 to 1990.
Cardiotoxicity, defined as congestive heart failure not due to other
causes, abnormal measurements of cardiac function that prompted
discontinuation of therapy, or sudden death from presumed cardiac causes,
was determined by a review of protocol records. RESULTS: Cardiotoxicity was
confirmed in 106 patients (1.6%): 58 had congestive heart failure, 43 had
changes in measures of cardiac function that prompted the discontinuation
of therapy, and five died suddenly from presumed cardiac causes. In a
multivariate analysis, factors that contributed to the relative risk (RR)
of toxicity were a cumulative anthracycline dose > or = 550 mg/m2 of
body-surface area (RR = 5.2), maximal dose > or = 50 mg/m2 (RR = 2.8),
female sex (RR = 1.9), black race (RR = 1.7), presence of trisomy 21 (RR =
3.4), and exposure to amsacrine (RR = 2.6). Cardiotoxicity within 1 year
after the completion of anthracycline treatment (early cardiotoxicity)
represented 89.5% of all cases. CONCLUSION: Early clinical cardiotoxicity
in children treated with anthracycline is rare. A high maximal dose, or
cumulative dose of anthracycline, female sex, black race, presence of
trisomy 21, and treatment with amsacrine increase the risk for
anthracycline- associated cardiotoxicity.
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