Abstract P1-11-02: Meta-regression and meta-analysis of dexrazoxane for cardioprotection in all breast cancer stages in patients treated with anthracyclines
Authors: Macedo AV , Rodrigues AN , Brant RC , Ribeiro AL 
Published: May 2019

Abstract
Background: Anthracyclines continue to be a valuable option in chemotherapy for breast cancer (BC), in spite of their well-documented cardiotoxicity. Anthracycline-induced cardiotoxicity depends on cumulative dose, and it actually begins with the first dose. Clinical studies have suggested that dexrazoxane could reduce this toxicity. Dexrazoxane is frequently used when higher anthracycline cumulative doses are needed, but is often omitted in the adjuvant setting. We aimed to analyse by an updated meta-analysis the cardioprotective effect of dexrazoxane in all BC stages in patients receiving anthracycline-based chemotherapy. In addition, we perfomed subgroup analyses and meta-regression to assess if the average anthracycline dose and the studies publication date would interfere in the cardiac event outcome.
Methods: We performed a systematic review and meta-analysis. The review was registered in PROSPERO database (CRD42017077462). We searched data from 1990 to August 2017 in Cochrane Central Register of Controlled Trials, Google Scholar, MEDLINE/Pubmed, LILACS, Web of Science, articles references and ASCO proceedings. Studies assessing congestive heart failure and cardiac event (cardiac function alterations without cardiac symptoms or hospitalization for cardiac reasons) as primary endpoints were included. Two reviewers independently performed the studies selection, risk of bias assessment and data extraction. Meta-analysis was done using random effect model for estimation of treatment effect. Heterogeneity was assessed by visual inspection of forest plots and by Q test. Subgroup analyses were carried out, according with the chemotherapy regimen (use of anthracycline in previous chemotherapy). In the meta-regression we used the random effects model.
Results: Our search resulted in 1603 articles, from which we included 7 studies providing 1545 participants. Meta-analysis showed an overall beneficial effect of dexrazoxane on reducing the risk of cardiac events (OR 0.262, CI 95%:0.169-0.407, p &lt; 0.0001). In two of the seven studies which evaluated the cardiac event outcome, the patients were previously exposed to anthracyclines. In this patients' subgroup, we found an odds ratio of 0,244 (CI 95%, 0,102 to 0,584). In the study subgroup that the patients didn't report previous exposure to anthracycline, the odds ratio was 0,266 (CI 95%, 0,149 to 0,478). The Q test to evaluate the difference between the subgroups showed a value of 0,026 with p = 0,871 suggesting there was no difference between the subgroups. The multiple meta-regression was performed, adding to the model the average dose and studies age variables, for a combined analysis. The statistical analysis of the impact of the two combined cofactors didn't show significative association (Q test = 2,36, df = 2 and p = 0,30).
Conclusions: Dexrazoxane reduced the occurrence of cardiac events when added to anthracycline based chemotherapy regimen. There was no evidence that the benefit of the reduction of cardiac events with the use of dexrazoxane was different according to the use of anthracycline in previous chemotherapy or by the used average dose of anthracycline. These findings may have significant implications for clinical practice.
Citation Format: Macedo AV, Rodrigues AN, Brant RC, Ribeiro AL. Meta-regression and meta-analysis of dexrazoxane for cardioprotection in all breast cancer stages in patients treated with anthracyclines [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-02.