Subacute cardiotoxicity caused by anthracycline therapy in children: can dexrazoxane prevent this effect?

Anthracyclines are potent cytostatic drugs, but their use may be limited by cardiac toxicity. In the study reported here, we investigated the incidence and outcome of anthracycline-induced cardiotoxicity and the possible preventive role of dexrazoxane. A total of 108 patients with the diagnosis of osteosarcoma, Ewing-sarcoma, soft tissue sarcoma and leukemia were studied between 1991 and 2003. Of these, 41 children (treated from 1996) received dexrazoxane (Group D) as chemotherapy from the beginning of their treatment (mean follow-up: 8.2±3.9 years). The dose of dexrazoxane was 20-fold higher than the anthracycline dose and was administered as a 20-min sodium-lactate infusion. The control (Group C) cohort comprised 67 children (all treated before 1996) who did not receive any cardioprotection (mean follow-up: 12.3±3.2 years). All patients in the C and D groups received anthracyclines in the form of short infusions (1–3 h). The cumulative dose of anthracycline did not differ between the two groups (Table 1). Supportive treatment did not change during the investigated period. Cardiac ultrasound examinations were performed regularly, and fractional shortening (FS) for detecting left ventricular function was measured. The incidence of acute cardiotoxicity was 13.4% in Group C patients and 7.3% in Group D patients, a nonsignificant difference. Cardiac function, expressed as FS, was abnormally low (<30%) 2 years after therapy in 13.7% of the Group C patients and in 0% of the Group D patients (p=0.034) (Fig. 1a) and was still abnormally low 3 years after therapy in 19.3% of the Group C patients and 0% of the Group D patients (p=0.008) (Fig. 1b). At the 5year follow-up, FS was under 30% in 14.9% of the Group C patients and 2.4% of the Group D patients (Fig. 1c). Seven patients in Group C needed heart-protective drugs (digitalis, furosemide, angiotensine converting enzyme inhibitors) for congestive heart failure for at least 6 months. Only one patient in Group D received cardiac drugs. Dilatative cardiomyopathy is a severe complication of anthracycline therapy, and even in children, lower cumulative doses (<300 mg/m 2 ) may cause irreversible congestive heart failure [3]. The incidence of slight cardiotoxicity has been reported to vary between 12 and 32% and mortality or severe dysfunction to vary between 2 and 7%, depending