Jones, Robin LWagner, Andrew JKawai, AkiraTamura, KazuoShahir, AshwinVan Tine, Brian AMartín-Broto, JavierPeterson, Patrick MWright, JenniferTap, William D2023-02-092023-02-092021-02-25http://hdl.handle.net/10668/17239Few prospective studies have assessed anthracycline-associated cardiotoxicity in patients with sarcoma. We evaluated cardiotoxicity in patients with soft-tissue sarcomas administered doxorubicin in the phase III ANNOUNCE trial (NCT02451943). Patients were anthracycline-naïve adults with locally advanced or metastatic disease and left ventricular ejection fraction (LVEF) ≥50%. Patients could receive eight cycles of doxorubicin at 75 mg/m2. The cardioprotectant, dexrazoxane, was allowed at investigator discretion. Symptomatic cardiac adverse events (AEs) were recorded using Medical Dictionary for Regulatory Activities and graded using Common Terminology Criteria for Adverse Events 4.0. LVEF deterioration was measured by echocardiogram or multigated acquisition scan, defined as a decrease to 10%. A total of 504 patients received ≥1 cycles of doxorubicin [median cumulative dose, 450.3 mg/m2 (range, 72.3-634.0)]. Median follow-up of cardiac AEs was 28 weeks. Dexrazoxane was coadministered more frequently to patients receiving higher cumulative doxorubicin doses (38.6% receiving Although follow-up was short, these results suggest doxorubicin can be administered at high cumulative doses (>450 mg/m2), with a low rate of cardiotoxicities, in the context of dexrazoxane coadministration.See related commentary by Benjamin and Minotti, p. 3809.enAdultAgedAged, 80 and overAntibiotics, AntineoplasticCardiotoxicityDouble-Blind MethodDoxorubicinFemaleHumansMaleMiddle AgedNeoplasm StagingProspective StudiesRetrospective StudiesSarcomaSoft Tissue NeoplasmsVentricular Function, Leftresearch article33632930open access10.1158/1078-0432.CCR-20-45921557-3265PMC8282740https://aacrjournals.org/clincancerres/article-pdf/27/14/3861/3087378/3861.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282740/pdf