MULTICENTER RANDOMIZED CONTROLLED CLINICAL-TRIAL TO EVALUATE CARDIOPROTECTION OF DEXRAZOXANE VERSUS NO CARDIOPROTECTION IN WOMEN RECEIVING EPIRUBICIN CHEMOTHERAPY FOR ADVANCED BREAST-CANCER

Purpose: Dexrazoxane was found effective in reducing doxorubicin cardi otoxicity 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 dexra zoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicit y. 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 cyclopho sphamide 600 mg/m(2) intravenously (IV), epirubicin 60 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV, on day 1 every 3 weeks. The other patien ts were treated with epirubicin 120 mg/m(2) IV on day 1 every 3 weeks, Cardiac toxicity was defined as clinical signs of congestive heart fa ilure, a decrease in resting left ventricular ejection fraction (LVEF) to less than or equal to 45%, or a decrease from baseline resting LVE F of greater than or equal to 20 EF units. Results: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patie nts (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazox ane arm. The cumulative probability of developing cardiotoxicity was s ignificantly lower in dexrazoxane-treated patients than in central pat ients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survi val, and overall survival were similar in both arms. Conclusion: Dexra zoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects a gainst epirubicin-induced cardiotoxicity and does not affect the clini cal activity and the noncardiac toxicity of epirubicin. The clinical u se of dexrazoxane should be recommended in patients whose risk of deve loping cardiotoxicity could hamper the eventual use and possible benef it of epirubicin. (C) 1996 by American Society of Clinical Oncology.