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Dexrazoxane role in the prevention of anthracycline cardiotoxicity in children with acute leukemia: a meta-analysis
Session:
CO 26 - Populações especiais
Speaker:
José Pedro Sousa
Congress:
CPC 2021
Topic:
K. Cardiovascular Disease In Special Populations
Theme:
30. Cardiovascular Disease in Special Populations
Subtheme:
30.6 Cardio-Oncology
Session Type:
Comunicações Orais
FP Number:
---
Authors:
José Pedro Sousa; Luís Puga; João Gameiro; Ana Rita Gomes; Carolina Saleiro; Diana de Campos; Carolina Lourenço; Lino Gonçalves
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Background: Anthracyclines have played a central role in improving the overall survival of acute leukemia patients. However, cardiotoxic side effects limit its net benefit. Dexrazoxane has been proved cardioprotective in the setting of low-dose anthracycline exposure, but its value in children, who are expected to receive high cumulative dosages, remains elusive.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Purpose: To perform a meta-analysis intended to appraise the efficacy and safety of dexrazoxane in pediatric acute leukemia patients managed with anthracycline chemotherapy.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Methods: We systematically searched MEDLINE, Embase, Web of Science, Cochrane CENTRAL and Google Scholar databases, using the terms "leukemia", "anthracycline" and "dexrazoxane", from inception to June 21st, 2020. Studies targeting cardiac events, subclinical cardiotoxicity, primary cancer progression or relapse, secondary malignancy, drug-associated adverse effects and mortality were included. The primary endpoint was a composite of incidental heart failure, left ventricular systolic function deterioration, significant ventricular arrhythmias and cardiovascular (CV) mortality. Investigational arms were those of dexrazoxane and no drug or placebo. A random-effects model with Mantel-Haenszel method was performed to calculate pooled ORs.</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Results: We encompassed 9 studies, of which 6 were prospective, including 5 randomized controlled trials (RCTs), albeit from only 2 databases. 5 studies focused on pediatric acute lymphoblastic leukemia patients, while 3 addressed children with acute myeloid leukemia, with 1 study covering both patient populations. Doxorubicin was the most represented anthracycline. 2375 patients were included, of whom 838 were under dexrazoxane. There were 47 primary endpoint events, including 6 CV deaths. Additionally, 177 failed primary cancer responses to treatment, 19 secondary malignant neoplasms and 63 chemotherapy-related deaths were reported. Dexrazoxane was found to numerically reduce both the primary endpoint (5 studies, OR 0.29, 95% CI 0.08-1.03, P 0.06, i<sup>2</sup> 0%) and CV mortality (3 studies, OR 0.47, 95% CI 0.04-5.46, P 0.55, i<sup>2</sup> 0%) and to significantly decrease subclinical cardiotoxicity, assessed as serum cardiac troponin T elevation (2 studies, OR 0.19, 95% CI 0.1-0.35, P <0.00001, i<sup>2</sup> 0%). Primary cancer outcome and the risk of secondary malignancy did not differ significantly between the 2 arms (3 studies, OR 0.84, 95% CI 0.59-1.18, P 0.3, i<sup>2</sup> 0% and 5 studies, OR 1.98, 95% CI 0.74-5.33, P 0.18, i<sup>2</sup> 0%, respectively). Likewise, severe mucositis and chemotherapy-related mortality were similar in both groups (2 studies, OR 0.97, 95% CI 0.29-3.22, P 0.96, i<sup>2</sup> 82%, and 4 studies, OR 1.15, 95% CI 0.57-2.31, P 0.7, i<sup>2</sup> 0%, respectively).</span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif">Conclusion: Dexrazoxane seems to maintain its cardioprotective properties and its ability not to deteriorate major cancer outcomes in pediatric acute leukemia patients.</span></span></p>
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