Aspects pédiatriques de la toxicité cardiaque des anthracyclines et implications pratiques pour sa prévention

Discovered during the sixties, anthracycline antibiotics are today widely used anti-cancer drugs. Their potentially fatal cardiac toxicity, which is related in part to the total cumulative dose, has been described since 1967. The aim of this paper is to describe their biological and clinical toxic effects on the heart, especially of children, and to propose prevention guidelines. The mechanisms of cardiac toxicity, with their destructive consequences on functional myocytes reserve, are shortly recalled. Acute, sub-acute and chronic clinical aspects of anthracycline's cardiomyopathy are the subject of a literature review. In Pediatric Oncology, the prolonged survival usually observed allows delayed congestive heart failure to occur by myocardial reserve insufficiency, as hemodynamic needs are quickly increasing, especially at the end of the somatic growth. Furthermore, the frequency of cardiac abnormalities is increasing with time after therapy, reaching about half of the explored patients after 15 years. The main known methods to prevent such a toxicity are reviewed. The parcimonious use of anthracyclines is already seen in children. Every method to decrease the maximal plasma concentration of the drug (weekly schedule or prolonged infusion) has to be considered. The active cardioprotectant agent such as ICRF-187, is in clinical development. Detection, prevention, and therapy of cardiac abnormalities, which are likely to precede delayed heart failure, still remains a difficult problem in these more and more numerous children to be cured of cancer.