Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients.
The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2-17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234+/-58 mg/m(2), median 240 mg/m(2) versus 203+/-86 mg/m(2), median 210 mg/m(2), P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m(2) of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group.


CONCLUSIONS
Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups.
Elbl
Lubomir
L
Department of Cardiology, University Hospital Brno, Jihlavska 20, 62500 Brno, Czech Republic. lelbl@fnbrno.cz
Hrstkova
Hana
H
Tomaskova
Iva
I
Blazek
Bohumir
B
Michalek
Jaroslav
J
D000293:Adolescent; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018153:Czech Republic; D003630:Daunorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D025401:Echocardiography, Stress; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011446:Prospective Studies; D011929:Razoxane / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D011929:Razoxane; D004317:Doxorubicin; D003630:Daunorubicin