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

ICOS-ONE Study Investigators, Daniela Cardinale, Fabio Ciceri, Roberto Latini, Maria Grazia Franzosi, Maria Teresa Sandri, Maurizio Civelli, Gian Franco Cucchi, Elisabetta Menatti, Maurizio Mangiavacchi, Raffaele Cavina, Enrico Barbieri, Stefania Gori, Alessandro Colombo, Giuseppe Curigliano, Michela Salvatici, Antonio Rizzo, Francesco Ghisoni, Alessandra Bianchi, Cristina Falci & 31 others Michele Aquilina, Andrea Rocca, Anna Monopoli, Carlo Milandri, Giuseppe Rossetti, Marco Bregni, Marco Sicuro, Alessandra Malossi, Daniele Nassiacos, Claudio Verusio, Monica Giordano, Lidia Staszewsky, Simona Barlera, Serge Masson, Carlo M. Cipolla, A. P. Maggioni, M. Tettamanti, C. Pellegrini, G. Scognamiglio, G. Corrado, F. De Rosa, S. Callegari, C. Fodor, R. Mazza, E. Sala, G. Fragasso, A. Farolfi, D. Andreis, A. Banzato, E. Gervasi, B. Barco

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)126-137
Number of pages12
JournalEuropean Journal of Cancer
Volume94
DOIs
Publication statusPublished - May 1 2018

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Enalapril
Troponin
Anthracyclines
Multicenter Studies
Cardiotoxicity
Drug Therapy
Epirubicin
Incidence
Doxorubicin
Early Diagnosis
Neoplasms
Electrocardiography
Hypertension

Keywords

  • Anthracyclines, Cancer chemotherapy, Cardiotoxicity, Clinical trial, Enalapril, Troponin

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Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. / Investigators, ICOS-ONE Study; Cardinale, Daniela; Ciceri, Fabio; Latini, Roberto; Franzosi, Maria Grazia; Sandri, Maria Teresa; Civelli, Maurizio; Cucchi, Gian Franco; Menatti, Elisabetta; Mangiavacchi, Maurizio; Cavina, Raffaele; Barbieri, Enrico; Gori, Stefania; Colombo, Alessandro; Curigliano, Giuseppe; Salvatici, Michela; Rizzo, Antonio; Ghisoni, Francesco; Bianchi, Alessandra; Falci, Cristina; Aquilina, Michele; Rocca, Andrea; Monopoli, Anna; Milandri, Carlo; Rossetti, Giuseppe; Bregni, Marco; Sicuro, Marco; Malossi, Alessandra; Nassiacos, Daniele; Verusio, Claudio; Giordano, Monica; Staszewsky, Lidia; Barlera, Simona; Masson, Serge; Cipolla, Carlo M.; Maggioni, A. P.; Tettamanti, M.; Pellegrini, C.; Scognamiglio, G.; Corrado, G.; De Rosa, F.; Callegari, S.; Fodor, C.; Mazza, R.; Sala, E.; Fragasso, G.; Farolfi, A.; Andreis, D.; Banzato, A.; Gervasi, E.; Barco, B.

In: European Journal of Cancer, Vol. 94, 01.05.2018, p. 126-137.

Research output: Contribution to journalArticle

Investigators, ICOS-ONE Study ; Cardinale, Daniela ; Ciceri, Fabio ; Latini, Roberto ; Franzosi, Maria Grazia ; Sandri, Maria Teresa ; Civelli, Maurizio ; Cucchi, Gian Franco ; Menatti, Elisabetta ; Mangiavacchi, Maurizio ; Cavina, Raffaele ; Barbieri, Enrico ; Gori, Stefania ; Colombo, Alessandro ; Curigliano, Giuseppe ; Salvatici, Michela ; Rizzo, Antonio ; Ghisoni, Francesco ; Bianchi, Alessandra ; Falci, Cristina ; Aquilina, Michele ; Rocca, Andrea ; Monopoli, Anna ; Milandri, Carlo ; Rossetti, Giuseppe ; Bregni, Marco ; Sicuro, Marco ; Malossi, Alessandra ; Nassiacos, Daniele ; Verusio, Claudio ; Giordano, Monica ; Staszewsky, Lidia ; Barlera, Simona ; Masson, Serge ; Cipolla, Carlo M. ; Maggioni, A. P. ; Tettamanti, M. ; Pellegrini, C. ; Scognamiglio, G. ; Corrado, G. ; De Rosa, F. ; Callegari, S. ; Fodor, C. ; Mazza, R. ; Sala, E. ; Fragasso, G. ; Farolfi, A. ; Andreis, D. ; Banzato, A. ; Gervasi, E. ; Barco, B. / Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial. In: European Journal of Cancer. 2018 ; Vol. 94. pp. 126-137.
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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.",
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author = "Investigators, {ICOS-ONE Study} and Daniela Cardinale and Fabio Ciceri and Roberto Latini and Franzosi, {Maria Grazia} and Sandri, {Maria Teresa} and Maurizio Civelli and Cucchi, {Gian Franco} and Elisabetta Menatti and Maurizio Mangiavacchi and Raffaele Cavina and Enrico Barbieri and Stefania Gori and Alessandro Colombo and Giuseppe Curigliano and Michela Salvatici and Antonio Rizzo and Francesco Ghisoni and Alessandra Bianchi and Cristina Falci and Michele Aquilina and Andrea Rocca and Anna Monopoli and Carlo Milandri and Giuseppe Rossetti and Marco Bregni and Marco Sicuro and Alessandra Malossi and Daniele Nassiacos and Claudio Verusio and Monica Giordano and Lidia Staszewsky and Simona Barlera and Serge Masson and Cipolla, {Carlo M.} and Maggioni, {A. P.} and M. Tettamanti and C. Pellegrini and G. Scognamiglio and G. Corrado and {De Rosa}, F. and S. Callegari and C. Fodor and R. Mazza and E. Sala and G. Fragasso and A. Farolfi and D. Andreis and A. Banzato and E. Gervasi and B. Barco",
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TY - JOUR

T1 - Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one trial

AU - Investigators, ICOS-ONE Study

AU - Cardinale, Daniela

AU - Ciceri, Fabio

AU - Latini, Roberto

AU - Franzosi, Maria Grazia

AU - Sandri, Maria Teresa

AU - Civelli, Maurizio

AU - Cucchi, Gian Franco

AU - Menatti, Elisabetta

AU - Mangiavacchi, Maurizio

AU - Cavina, Raffaele

AU - Barbieri, Enrico

AU - Gori, Stefania

AU - Colombo, Alessandro

AU - Curigliano, Giuseppe

AU - Salvatici, Michela

AU - Rizzo, Antonio

AU - Ghisoni, Francesco

AU - Bianchi, Alessandra

AU - Falci, Cristina

AU - Aquilina, Michele

AU - Rocca, Andrea

AU - Monopoli, Anna

AU - Milandri, Carlo

AU - Rossetti, Giuseppe

AU - Bregni, Marco

AU - Sicuro, Marco

AU - Malossi, Alessandra

AU - Nassiacos, Daniele

AU - Verusio, Claudio

AU - Giordano, Monica

AU - Staszewsky, Lidia

AU - Barlera, Simona

AU - Masson, Serge

AU - Cipolla, Carlo M.

AU - Maggioni, A. P.

AU - Tettamanti, M.

AU - Pellegrini, C.

AU - Scognamiglio, G.

AU - Corrado, G.

AU - De Rosa, F.

AU - Callegari, S.

AU - Fodor, C.

AU - Mazza, R.

AU - Sala, E.

AU - Fragasso, G.

AU - Farolfi, A.

AU - Andreis, D.

AU - Banzato, A.

AU - Gervasi, E.

AU - Barco, B.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - Anthracyclines, Cancer chemotherapy, Cardiotoxicity, Clinical trial, Enalapril, Troponin

U2 - 10.1016/j.ejca.2018.02.005

DO - 10.1016/j.ejca.2018.02.005

M3 - Article

VL - 94

SP - 126

EP - 137

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

ER -