Cor Vasa 2005, 46(12):454-461

The effect of dexrazoxane (icrf-187) administration on the incidence of late cardiotoxicity in patients treated with anthracyclins for childhood hematological malignancy: prospective echocardiographic follow-up.

Lubomír Elbl^1,*, Hana Hrstková², Iva Tomášková¹, Bohumír Blažek³, Jaroslav Michálek²

¹ Oddělení funkčního vyšetřování

² 1. dětská interní klinika, Fakultní nemocnice Brno, Brno

³ Dětská klinika, Fakultní nemocnice s poliklinikou, Ostrava-Poruba, Česká republika

Aim of study:
The authors conducted a prospective, non-randomized 8-year study designed to assess the cardioprotective effect of dexrazoxane (ICRF-187) against late myocardial injury by anthracyclins in patients treated for hematological malignancy in childhood.

Patients and methods:
The follow-up included 75 patients (40 boys/35 girls) aged 2-17 (median 6.5) years at the time of diagnosis. Dexrazoxane was administered before each cycle of chemotherapy with anthracyclin in 53 patients (26 boys/
27 girls) and standard protocol was used in 22 patients (14 boys/8 girls). Echocardiography was undertaken prior to chemo-therapy, after its completion, and annually for eight years. Dynamic exercise echocardiography was performed in the last year of follow-up.

Results:
Higher cumulative anthracyclin doses were given in the cardioprotection subgroup (234 ± 58, median 240 mg/m2 vs. 203 ± 86, median 210 mg/m2; p < 0.04), where also a higher number of patients received higher cumulative doses ≥ 240 mg/m2 of anthracyclins (p < 0.05). During follow-up, there was a progressive decrease in ejection fraction (EF) and fractional shortening (FS) in both subgroups, with a progressive decrease in either marker seen in the subgroup without cardioprotection and reaching a significant difference at eight years compared with the cardioprotection subgroup (p < 0.05). An abnormal decline in either marker > 10% compared with baseline was observed in 24% of all patients; 41% of patients were non-cardio-protection subgroup patients while 19% belonged to the cardioprotection subgroup (p < 0.01). When undergoing exercise testing, patients without cardioprotection vs. those with cardioprotection showed lower resting EF and cardiac index values (CI) (p < 0.05). Still, the exercise testing values did not differ significantly. The cardioprotection subgroup included more patients with very good exercise tolerance > 3 W/kg and significantly fewer patients with reduced tolerance < 2 W/kg (p < 0.05) compared with the non-cardioprotection subgroup.

Conclusion:
Dexrazoxane reduces the incidence of subclinical myocardial injury during eight-year follow-up. Clinical signs of cardiotoxicity were not seen in either subgroup. Patients with cardioprotection showed better exercise tolerance, but the hemodynamic response to exercise did not vary between the subgroups.

Keywords: Dexrazoxane; Anthracyclins; Cardioprotection; Cardiotoxicity; Echocardiography

Published: December 1, 2005  Show citation