TY - JOUR
T1 - Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer
AU - Venturini, M.
AU - Michelotti, A.
AU - Del Mastro, L.
AU - Gallo, L.
AU - Carnino, F.
AU - Garrone, O.
AU - Tibaldi, C.
AU - Molea, N.
AU - Bellina, R. C.
AU - Pronzato, P.
AU - Cyrus, P.
AU - Vinke, J.
AU - Testore, F.
AU - Guelfi, M.
AU - Lionetto, R.
AU - Bruzzi, P.
AU - Conte, P. F.
AU - Rosso, R.
PY - 1996
Y1 - 1996
N2 - Purpose: Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane:doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. Patients and Methods: One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV an day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to ≤ 45%, or a decrease from baseline resting LVEF of ≤ 20 EF units. Results: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxane arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. Conclusion: Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin- induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.
AB - Purpose: Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane:doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. Patients and Methods: One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV an day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to ≤ 45%, or a decrease from baseline resting LVEF of ≤ 20 EF units. Results: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxane arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. Conclusion: Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin- induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.
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M3 - Article
C2 - 8955656
AN - SCOPUS:10544231456
VL - 14
SP - 3112
EP - 3120
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 12
ER -