Comparisons of Cardiotoxicity and Efficacy of Anthracycline-Based Therapies in Breast Cancer: A Network Meta-Analysis of Randomized Clinical Trials

The effects of anthracycline-based chemical therapies on breast cancer are controversial and inconclusive. We undertook a network meta-analysis to assess the cardiotoxicity and effects of anthracycline therapies in breast cancer. The PubMed, Embase, and Cochrane databases up to August 2018 were reviewed. We identified 19 randomized clinical trials including 3,484 patients with breast cancer which assessed both cardiotoxicity and the effects of anthracycline-based therapies. Eligible studies included the following five treatment strategies: doxorubicin, epirubicin, liposomal doxorubicin (LD), doxorubicin + dexrazoxane (DD), and epirubicin + dexrazoxane (ED). In a direct meta-analysis, epirubicin, LD, DD, and ED had significantly superior cardioprotective effects compared with doxorubicin with odds ratios and 95% CIs of 1.64 (1.04, 2.57), 3.75 (2.46, 5.70), 2.88 (1.93, 4.29), and 3.66 (1.09, 12.33), respectively. Doxorubicin showed no significant difference of response rate compared with epirubicin or LD or DD, respectively. In a network meta-analysis, the ranking order of cardiotoxicity was doxorubicin (worst), epirubicin, DD, LD, and ED (best). The ranking order of the response rate was LD (best), doxorubicin, epirubicin, ED, and DD (worst). The most favorable balance between benefit and risk was shown for ED (best) followed by LD, DD, epirubicin, and doxorubicin. In conclusion, LD or ED is the suitable anthracycline treatment for breast cancer in consideration of both cardiotoxicity and efficacy.