Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up.
BACKGROUND
The authors conducted a retrospective study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for hematological malignancy.


METHODS
The authors examined 108 patients (63 male, 45 female) 5-29 years old, (median 15 years). All patients were in long-term remission of their malignancy. The cardioprotection was given to 68 patients (39 male, 29 female), and standard treatment was used in 40 patients (24 male, 16 female). Dexrazoxane (cardioxane, Chiron Company, The Netherlands) was given in 20:1 ratio to anthracycline. The follow-up time was 2-20 years (mean 7 years). The control group consisted of 41 volunteers (22 males, 19 females) 4-31 years old (median 18 years). The cardiotoxicity has been defined as the presence of heart failure or the decline of shortening fraction below 30% or ejection fraction (EF) below 55%. The end-systolic wall stress (ESS), myocardial performance index (MPI; Tei index), and parameters of left ventricular diastolic filling were also assessed.


RESULTS
The anthracycline cardiomyopathy with the presence of heart failure was diagnosed in only one patient treated with a standard regimen. The pathological decline of fractional shortening was present in three (5%) and six (15%) patients with and without cardioprotection given, respectively. Similarly, none of the patients with cardioprotection revealed a pathological value of EF, while four (10%) patients without cardioprotection showed an EF decrease. Finally, ESS and isovolumic relaxation time were pathologically increased in the group without cardioprotection in comparison to the controls and to the group with cardioprotection. However, the MPI was significantly increased in both groups of patients.


CONCLUSIONS
Dexrazoxane reduces the risk of late clinical and subclinical cardiotoxicity and does not affect the response rates to chemotherapy and overall survival during the median follow-up period of 7 years (follow-up period 2-20 years).
Elbl
Lubomir
L
Department of Cardiopulmonary Testing, University Hospital Brno, Jihlavska 20, Brno, 62500, Czech Republic. lelbl@fnbrno.cz
Hrstkova
Hana
H
Tomaskova
Iva
I
Michalek
Jaroslav
J
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000517:prevention & control*; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D008297:Male; D011929:Razoxane / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D013318:Stroke Volume / Q000187:drug effects; D016019:Survival Analysis; D016896:Treatment Outcome
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002317:Cardiovascular Agents; D011929:Razoxane