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. 2019 Sep 24;1(1):68-79.
doi: 10.1016/j.jaccao.2019.08.003. eCollection 2019 Sep.

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer

Ariane V S Macedo  1   2 , Ludhmila A Hajjar  3 , Alexander R Lyon  4 , Bruno R Nascimento  1 , Alessandro Putzu  5 , Lorenzo Rossi  6 , Rafael B Costa  2 , Giovanni Landoni  7   8 , Angélica Nogueira-Rodrigues  9 , Antonio L P Ribeiro  1
Affiliations

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer

Ariane V S Macedo et al. JACC CardioOncol. .

Abstract

Objectives: The authors performed a systematic review and meta-analysis of randomized and nonrandomized trials on the efficacy of dexrazoxane in patients with breast cancer who were treated with anthracyclines with or without trastuzumab.

Background: Breast cancer treatment with anthracyclines and trastuzumab is associated with an increased risk of cardiotoxicity. Among the various strategies to reduce the risk of cardiotoxicity, dexrazoxane is an option for primary prevention, but it is seldom used in clinical practice.

Methods: Online databases were searched from January 1990 up to March 1, 2019, for clinical trials on the use of dexrazoxane for the prevention of cardiotoxicity in patients with breast cancer receiving anthracyclines with or without trastuzumab. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model meta-analysis.

Results: Seven randomized trials and 2 retrospective trials with a total of 2,177 patients were included. Dexrazoxane reduced the risk of clinical heart failure (RR: 0.19; 95% CI: 0.09 to 0.40; p < 0.001) and cardiac events (RR: 0.36; 95% CI: 0.27 to 0.49; p < 0.001) irrespective of previous exposure to anthracyclines. The rate of a partial or complete oncological response, overall survival, and progression-free survival were not affected by dexrazoxane.

Conclusions: Dexrazoxane reduced the risk of clinical heart failure and cardiac events in patients with breast cancer undergoing anthracycline chemotherapy with or without trastuzumab and did not significantly impact cancer outcomes. However, the quality of available evidence is low, and further randomized trials are warranted before the systematic implementation of this therapy in clinical practice.

Keywords: ANT, anthracycline; BC, breast cancer; CI, confidence interval; CTX, cardiotoxicity; DEX, dexrazoxane; HER2, anti–human epidermal growth factor 2; HR, hazard ratio; RR, risk ratio; cardiomyopathy; cardioprotection; cardiotoxicity; dexrazoxane; doxorubicin; heart failure; meta-analysis; survivorship; trastuzumab.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Flow Diagram for the Selection of Studies A flow diagram of the studies screened, assessed for eligibility, and included in the review, with reasons for exclusions.
Figure 2
Figure 2
Risk of Bias Summary Authors' judgments about the risk of bias in each included randomized trial. Green symbol with + = low risk of bias; yellow symbol with question mark = unknown; red symbol with– = high risk of bias.
Figure 3
Figure 3
Forest Plot for the Effect of DEX on the Risk of Clinical Heart Failure and Cardiac Events in BC Patients Treated With ANTs Dexrazoxane (DEX) therapy reduced the risk of cardiac outcomes in patients receiving anthracycline (ANT)-based chemotherapy. CI = confidence interval; df = degree of freedom; M-H = Mantel-Haenszel.
Figure 4
Figure 4
Forest Plot for the Effect of DEX on Oncological Response in BC Patients Treated With ANTs Oncological outcomes were similar in groups exposed or not exposed to dexrazoxane. Abbreviations as in Figure 3.
Figure 5
Figure 5
Forest Plot for the Effect of DEX on the Overall Survival and Progression-Free Survival Overall survival and progression free-survival were similar between the groups. IV = inverse variance; other abbreviations as in Figure 3.
Central Illustration
Central Illustration
Dexrazoxane in Breast Cancer Patients Under Anthracycline-Based Chemotherapy The present systematic review was performed according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) , and the Cochrane Handbook for Systematic Reviews of Interventions . We identified, in a universe of breast cancer patients evaluated in clinical studies (blue and red people), the population included in this review (red people). Studies analyzing the cardioprotective effect of dexrazoxane in breast cancer patients treated with anthracyclines were selected for meta-analysis. In 9 studies with a total of 2,177 breast cancer patients, dexrazoxane reduced the risk of heart failure and cardiac events without a significantly impact in cancer outcomes.
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