Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer

Ariane V S Macedo; Ludhmila A Hajjar; Alexander R Lyon; Bruno R Nascimento; Alessandro Putzu; Lorenzo Rossi; Rafael B Costa; Giovanni Landoni; Angélica Nogueira-Rodrigues; Antonio L P Ribeiro

doi:10.1016/j.jaccao.2019.08.003

Efficacy of Dexrazoxane in Preventing Anthracycline Cardiotoxicity in Breast Cancer

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

Authors

Affiliations

¹ Department of Cardiology of Hospital das Clínicas, Federal University of Minas Gerais and Department of Internal Medicine, School of Medicine of Federal University of Minas Gerais, Belo Horizonte, Brazil.
² Oncoclínicas Group, Belo Horizonte, Brazil.
³ Department of Cardiopneumology of InCor and Division of Cardio-Oncology, Cancer Institute of Sao Paulo, School of Medicine of São Paulo University, São Paulo, Brazil.
⁴ Cardio-oncology Service, Royal Brompton Hospital and Imperial College London, United Kingdom.
⁵ Division of Anesthesiology, Department of Anesthesiology, Pharmacology, Intensive Care, and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.
⁶ Institute of Oncology of Southern Switzerland, Bellinzona, Switzerland.
⁷ Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.
⁸ Vita-Salute San Raffaele University, Milan, Italy.
⁹ Division of Oncology of Hospital das Clínicas, Federal University of Minas Gerais and Department of Internal Medicine, School of Medicine of Federal University of Minas Gerais, Belo Horizonte, Brazil.

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.