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

Abstract

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.

Age-Related Considerations in Cardio-Oncology

“…Because of its protective effect on acute cardiotoxicity, dexrazoxane is currently widely applied in clinical practise. 91,104 -106 Dexrazoxane leads to reduction of cardiac injury, as reflected by Troponin T levels 107 and echocardiographic parameters. 108 A multicenter randomized phase III study found a significant reduction in cardiac events (39% vs 13%) and congestive HF (11% vs 1%) with dexrazoxane in high-risk patients previously treated with anthracyclines.…”

“…88 In contrast, studies on the cardiotoxicity profile of epirubicin are inconclusive. While some studies suggest reduced cardiotoxicity by epirubicin in comparison with doxorubicin, 90,91 others mention isoequivalent toxicity profiles of the 2 anthracycline agents. 88 Beside these conventional therapies, efforts have been made to reduce cardiotoxicity by modifying the chemical structure of anthracyclines.…”

“…Currently, multiple pegylated liposomal anthracycline formulations are approved by the FDA or in clinical trials. 93 Randomized controlled trials (RCT) have shown that liposomal anthracyclines are less cardiotoxic compared to conventional formulations, 91,94 and have also shown to be beneficial in elderly patients. 93,[95][96][97] In a multicenter phase II trial in elderly (>60 years) with diffuse large B-cell lymphoma, patients received standard RCHOP therapy with pegylated liposomal doxorubicin instead of the "regular" formulation.…”

Abordaje de la enfermedad cardiovascular en mujeres con cáncer de mama. Posición de la Asociación Nacional de Cardiólogos de México (ANCAM)

“…Finally, therapies other than anthracyclines should be considered when they are superior or equally effective (e.g., docetaxel/ cyclophosphamide) for cases of BC. [146][147][148] Use of doxorubicin liposomal. There is an alternative formulation of either encapsulated doxorubicin or liposomal (instead of doxorubicin or in patients who have already exceeded doses).…”

Resistance to different anthracycline chemotherapeutics elicits distinct and actionable primary metabolic dependencies in breast cancer

“…Addressing this knowledge gap is important, as numerous monotherapy and combination therapy regimens are often available to treat each patient. Here, we show that breast cancer cells resistant to either doxorubicin or epirubicin, two anthracycline drugs that are used interchangeably for breast cancer treatment ( Mao et al, 2019 ), rely on distinct primary metabolic processes, and that exploiting these dependencies may impair the growth of treatment resistant breast cancers.…”