Literature DB >> 29567630

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial.

Daniela Cardinale1, Fabio Ciceri2, Roberto Latini3, Maria Grazia Franzosi4, Maria Teresa Sandri5, Maurizio Civelli6, GianFranco Cucchi7, Elisabetta Menatti8, Maurizio Mangiavacchi9, Raffaele Cavina10, Enrico Barbieri11, Stefania Gori12, Alessandro Colombo1, Giuseppe Curigliano13, Michela Salvatici5, Antonio Rizzo14, Francesco Ghisoni15, Alessandra Bianchi16, Cristina Falci17, Michele Aquilina18, Andrea Rocca19, Anna Monopoli20, Carlo Milandri21, Giuseppe Rossetti22, Marco Bregni23, Marco Sicuro24, Alessandra Malossi25, Daniele Nassiacos26, Claudio Verusio27, Monica Giordano28, Lidia Staszewsky4, Simona Barlera4, Enrico B Nicolis4, Michela Magnoli4, Serge Masson4, Carlo M Cipolla6.   

Abstract

BACKGROUND: Troponin changes over time have been suggested to allow for an early diagnosis of cardiac injury ensuing cancer chemotherapy; cancer patients with troponin elevation may benefit of therapy with enalapril. It is unknown whether a preventive treatment with enalapril may further increase the benefit.
METHODS: The International CardioOncology Society-one trial (ICOS-ONE) was a controlled, open-label trial conducted in 21 Italian hospitals. Patients were randomly assigned to two strategies: enalapril in all patients started before chemotherapy (CT; 'prevention' arm), and enalapril started only in patients with an increase in troponin during or after CT ('troponin-triggered' arm). Troponin was assayed locally in 2596 blood samples, before and after each anthracycline-containing CT cycle and at each study visit; electrocardiogram and echocardiogram were done at baseline, and at 1, 3, 6 and 12-month follow-up. Primary outcome was the incidence of troponin elevation above the threshold.
FINDINGS: Of the 273 patients, 88% were women, mean age 51 ± 12 years. The majority (76%) had breast cancer, 3% had a history of hypertension and 4% were diabetic. Epirubicin and doxorubicin were most commonly prescribed, with median cumulative doses of 360 [270-360] and 240 [240-240] mg/m2, respectively. The incidence of troponin elevation was 23% in the prevention and 26% in the troponin-triggered group (p = 0.50). Three patients (1.1%) -two in the prevention, one in the troponin-triggered group-developed cardiotoxicity, defined as 10% point reduction of LV ejection fraction, with values lower than 50%.
INTERPRETATION: Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient.
Copyright © 2018 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Anthracyclines; Cancer chemotherapy; Cardiotoxicity; Clinical trial; Enalapril; Troponin

Mesh:

Substances:

Year:  2018        PMID: 29567630     DOI: 10.1016/j.ejca.2018.02.005

Source DB:  PubMed          Journal:  Eur J Cancer        ISSN: 0959-8049            Impact factor:   9.162


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