Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography.
OBJECTIVE
To assess the late cardioprotective effect of dexrazoxane associated with doxorubicin during treatment of osteosarcoma by means of low-dose dobutamine stress echocardiography (LDDSE) in non-relapsed asymptomatic children and teenagers.


METHODS
The study population included 58 patients with osteosarcoma divided in three groups, with equivalent age range, gender proportion and body surface area. Group I (21 patients, 14 males, 15 +/- 4 years) was analyzed before chemotherapy and considered the control group; Group II (19 patients, 11 males, 19.7 +/- 4 years) was treated with 348.4 +/- 18 mg/m2 of doxorubicin only and Group III (18 patients, 14 male, 16.8 +/- 5 years) treated with 396.5 +/- 55 mg/m2 of doxorubicin with dexrazoxane in the ratio 10:1. The patients were submitted to LDDSE (maximal dose 5 microg/kg/min). No major side effects were observed. Heart rate, blood pressure, left ventricular diameters, end systolic wall stress (ESWS), and other diastolic and systolic function indexes were assessed at rest conditions and during LDDSE and compared between the three groups.


RESULTS
Group III received a doxorubicin dose significantly greater than Group II (P = 0.001). During LDDSE there were no significant changes in the diastolic function indexes in any of the groups, but there was a significant increase of systolic indexes and a decrease of ESWS in Group III compared to group II. There was no significant difference of any systolic functional parameters between Group I and III. Considering the ejection fraction (EF) at rest or at LDDSE, 13 patients (69.4%) in Group II and 5 patients (27.7%) in Group III were considered to have systolic dysfunction. (P = 0.02).


CONCLUSIONS
Myocardial response to LDDSE in patients treated with doxorubicin and dexrazoxane was similar to patients without chemotherapy and better than those treated with doxorubicin only, suggesting less cardiotoxicity.
Paiva
Marcelo G
MG
Department of Cardiology, Federal University of São Paulo, EPM-UNIFESP-São Paulo, Brazil. mgpaiva@cardio.br
Petrilli
Antônio S
AS
Moisés
Valdir A
VA
Macedo
Carla Renata Donato
CR
Tanaka
Cristiana
C
Campos
Orlando
O
D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002648:Child; D004280:Dobutamine / Q000494:pharmacology*; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology*; D004336:Drug Antagonism; D025401:Echocardiography, Stress / Q000379:methods; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011929:Razoxane / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D004280:Dobutamine; D011929:Razoxane; D004317:Doxorubicin