Comparison of epirubicin and doxorubicin cardiotoxicity induced by low doses: evolution of the diastolic and systolic parameters studied by radionuclide angiography.
BACKGROUND
Previous studies have demonstrated that epirubicin (EPI) has a lower propensity to produce cardiotoxic effects than doxorubicin (DXR) at high doses.


OBJECTIVE
The aim of the study was to compare the cardiotoxicity induced by low doses of EPI and DXR in patients before and 1 month after the end of chemotherapy.


METHODS
In a prospective study, 99 patients with a mean age of 51 +/- 12 years and without cardiac disease were studied before and 1 month after the end of chemotherapy. Group 1 included 38 patients receiving 246 +/- 96 mg/m2 of DXR and Group 2 included 61 patients receiving EPI with and equivalent dose of 219 +/- 92 mg/m2 of DXR. Ejection fraction (EF) of the left ventricle (LV), peak ejection rate (PER), and peak filling rate (PFR) [expressed in end-diastolic volume/s (EDV/s)] were evaluated by gated radionuclide angiography; PFR/PER were also calculated.


RESULTS
Moderate and similar alterations of left ventricular ejection fraction were shown for low doses of anthracyclines. The EF of the LV decreased from 57 +/- 6% to 54 +/- 6% for DXR group (Group 1) (p = 0.005), and from 58 +/- 5% to 55 +/- 5% for the EPI group (Group 2)(p = 0.001). The PER of the left ventricle fell from 3.08 +/- 0.46 EDV/s to 2.79 +/- 0.49 in Group 1 (p = 0.004) and from 2.98 +/- 0.50 to 2.73 +/- 0.34 EDV/s in Group 2 (p = 0.001). In contrast, no significant alteration of PFR appeared in Group 2 (from 2.72 +/- 0.51 to 2.62 +/- 0.41 EDV/s) for the equivalent dose of anthracycline, while PFR of the LV dropped from 2.82 +/- 0.76 (EDV/s) to 2.41 +/- 0.55 after doxorubicin (p = 0.004). No difference was found between 1 and 12 months after the end of the treatment in 25 patients in Group 1 and 28 patients in Group 2. These results confirm the advantage of EPI over DXR in terms of cardiotoxicity and help explain the relationship of cellular damage mechanisms with the functional parameters of nuclear investigation.


CONCLUSIONS
A possible explanation for specific alteration after DXR could be the increased production of semiquinone free radicals, which are known to induce membrane damage and, consequently, myocardial edema and diastolic alteration.
Cottin
Y
Y
Centre de Cardiologie, Hôpital du Bocage, Dijon, France.
Touzery
C
C
Dalloz
F
F
Coudert
B
B
Toubeau
M
M
Riedinger
A
A
Louis
P
P
Wolf
J E
JE
Brunotte
F
F
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003971:Diastole / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013318:Stroke Volume / Q000187:drug effects; D013667:Technetium; D016277:Ventricular Function, Left / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D013667:Technetium; D004317:Doxorubicin