PEDIATRIC FEATURES OF ANTHRACYCLINES CARD IAC TOXICITY AND PRACTICAL IMPLICATIONS FOR PREVENTION

Discovered during the sixties anthracycline antibiotics are today wide ly used anti-cancer drugs. Their potentially fatal cardiac tonicity, w hich is related in part to the total cumulative dose, has been describ ed since 1967. The aim of this paper is to describe their biological a nd clinical toxic effects on the heart, especially of children, and to propose prevention guidelines. The mechanisms of cardiac toxicity, wi th their destructive consequences on functional myocytes reserve, are shortly recalled. Acute, sub-acute and chronic clinical aspects of ant hracycline's cardiomyopathy are the subject of a literature review. In Pediatric Oncology, the prolonged survival usually observed allows de layed congestive heart failure to occur by myocardial reserve insuffic iency, as hemodynamic needs are quickly increasing, especially at the end of the somatic growth. Furthermore, the frequency of cardiac abnor malities is increasing with time after therapy, reaching about half of the explored patients after 15 years. The main known methods to preve nt such a toxicity are reviewed. The parcimonious use of anthracycline s is already seen in children. Every method to decrease the maximal pl asma 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 fail ure, still remains a difficult problem in these more and more numerous children to be cured of cancer.