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Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

Rayson, D. ; Suter, T. M. ; Jackisch, C. ; van der Vegt, S. ; Bermejo, B. ; van den Bosch, J. ; Vivanco, G. L. ; van Gent, A. M. ; Wildiers, H. ; Torres, A. ; Provencher, L. ; Temizkan, M. ; Chirgwin, J. ; Canon, J. L. ; Ferrandina, G. ; Srinivasan, S. ; Zhang, L. ; Richel, D. J.

In: Annals of Oncology, 2012, vol. 23, no. 7, p. 1780-1788

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    Titre
    • Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial
    Auteur
    • Rayson, D.. Department of Medical Oncology, Dalhousie University, Halifax, Canada
    • Suter, T. M.. Department of Internal Medicine, Bern University Hospital, Bern, Switzerland
    • Jackisch, C.. Department of Obstetrics and Gynecology, Klinikum Offenbach GmbH, Offenbach, Germany
    • van der Vegt, S.. Department of Oncology, Mesos Medical Centre, Utrecht, The Netherlands
    • Bermejo, B.. Department of Hematology and Oncology, Hospital Clinico, Valencia, Spain
    • van den Bosch, J.. Albert Schweitzer Hospital, Dordrecht, The Netherlands
    • Vivanco, G. L.. Department of Medical Oncology, Hospital de Cruces, Cruces-Baracaldo, Spain
    • van Gent, A. M.. Amphia Hospital, Breda, The Netherlands
    • Wildiers, H.. Department of Oncology, UZ Gasthuisberg, Leuven, Belgium
    • Torres, A.. Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain
    • Provencher, L.. Department of Oncology, Hôpital du Saint Sacrement, Quebec, Canada
    • Temizkan, M.. Department of Medical Oncology, Ziekenhuis Sint Jansdal, Harderwijk, The Netherlands
    • Chirgwin, J.. Maroondah Hospital, Victoria, Australia
    • Canon, J. L.. Department of Medical Oncology, Grand Hôpital de Charleroi, Charleroi, Belgium
    • Ferrandina, G.. Department of Oncology, Catholic University, Campobasso, Italy
    • Srinivasan, S.. Merck & Co, Kenilworth, USA
    • Zhang, L.. Merck & Co, Kenilworth, USA
    • Richel, D. J.. Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Annals of Oncology, 2012, vol. 23, no. 7, p. 1780-1788. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:291798
    Summary
    Background The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Patients and methods Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) ≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Results Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C → T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H → T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). Conclusion PLD+C+H → T+H is feasible and results in lower early cardiotoxicity rates compared with A+C → T+H