Incidence of cardiotoxicity after high cumulative dose of anthracyclines in adult patients with advanced soft tissue sarcomas: A systematic review and meta-analysis.

Abstract

e24004 Background: The risk of anthracycline-related cardiotoxicity increases with cumulative dose, with most available literature based from studies on breast cancer patients. Although soft tissue sarcomas are heterogenous entities, anthracycline-based chemotherapy is considered the most active regimen. This study aims to clarify the incidence of cardiotoxicity among patients with advanced soft tissue sarcomas who receive a high cumulative dose of anthracyclines. Methods: We performed a systematic search across PubMed, Cochrane, Google Scholar, and ASCO and ESMO references. Studies were eligible if they (1) investigated soft tissue sarcoma patients, (2) receiving high cumulative doses of doxorubicin ( > 450mg/m2), lipodox ( > 550mg/m2) or epirubicin ( > 900mg/m2), and (3) reported the incidence of cardiotoxicity (clinical and subclinical). Three authors independently assessed validity of the articles using the Cochrane Tool for randomized trials and the Newcastle-Ottawa scale for cohorts. Pooled analysis was performed using MetaXL with the random effects model. Pooled incidence with 95% CI and heterogeneity (Cochran's Q) were determined. Results: For doxorubicin, 4 studies with 168 patients without pre-existing cardiomyopathy, and a mean age of 47 years were included. At a mean cumulative dose of 651.1mg/m2, clinical cardiotoxicity was seen in 2.6% (0.62–5.62%,Q3) while subclinical cardiotoxicity was seen in 23.8%(17.67%-30.53%,Q86). For epirubicin, we included 3 studies with 109 patients, without pre-existing cardiomyopathy, and mean age of 39 years. At a cumulative dose of 1128.33mg/m2, clinical cardiotoxicity was seen in 5.3% (1.74–10.38%,Q25), and subclinical cardiotoxicity was seen in 13.4% (7.62%-20.50%,Q37). Conclusions: The incidence of cardiotoxicity in patients with advanced soft tissue sarcomas receiving high cumulative dose of anthracyclines is comparable with existing data on breast, lymphoma and leukemia patients. Subclinical cardiotoxicity is more prominent. Majority of the patients received cardioprotective strategies during their treatment (dexrazoxane or continuous infusions of doxorubicin). Evidence with regard to lipodox is lacking.