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Therapy Insight: anthracyclines and trastuzumab—the optimal management of cardiotoxic side effects

Nature Clinical Practice Oncology volume 5, pages 324–335 (2008)Cite this article

Abstract

Anthracyclines and trastuzumab are key agents in the management of patients with breast cancer, and have revolutionized the management of both early-stage and advanced-stage disease. The use of anthracyclines, however, can be compromised by the potential for cardiotoxicity; trastuzumab also has the potential for causing cardiotoxicity in patients receiving concurrent or prior anthracyclines. Although its development is treatment limiting, cardiotoxicity can be minimized with appropriate clinical care and drug scheduling. We discuss the efficacy of trastuzumab, its potential for cardiac compromise, and its interaction with anthracyclines. We highlight biological mechanisms that might be responsible for cardiotoxicity, describe the established and trial schedules of both agents, and discuss clinical strategies used to minimize the risk of developing cardiac failure through appropriate scheduling of trastuzumab with anthracyclines.

Key Points

  • Anthracyclines are the precipitating factor for trastuzumab-induced cardiotoxicity and, therefore, anthracyclines and trastuzumab should not be given synchronously

  • Trastuzumab can usually be given safely following completion of adjuvant anthracycline-based chemotherapy, and trastuzumab-associated cardiotoxicity is usually treatable and reversible

  • Regular left-ventricular function monitoring before and during therapy is mandatory in all patients receiving adjuvant trastuzumab after anthracyclines

  • In patients with advanced disease, the clinical benefit from trastuzumab needs to be balanced against cardiotoxicity

  • Trastuzumab in combination with non-anthracycline chemotherapy does not seem to be associated with any increased risk of cardiotoxicity

  • The optimal duration for adjuvant trastuzumab therapy suggested by current data is 1 year, although some data support as little as 9 weeks of trastuzumab; however, scheduling trastuzumab before initiating adjuvant anthracycline therapy remains experimental and might be risky because of the long half-life of trastuzumab

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Acknowledgements

S Popat is in receipt of a Clinical Senior Lectureship Award from the Higher Education and Funding Council for England. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Authors and Affiliations

  1. S Popat is a Senior Lecturer in Medical Oncology at the Royal Marsden Hospital and Imperial College, London, UK,

    Sanjay Popat

  2. IE Smith is Professor of Cancer Medicine, at The Royal Marsden Hospital and Institute of Cancer Research, London, UK,

    Ian E Smith

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Correspondence to Ian E Smith.

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Competing interests

IE Smith receives Speakers Bureau honoraria from Roche. S Popat declared no competing interests.

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Popat, S., Smith, I. Therapy Insight: anthracyclines and trastuzumab—the optimal management of cardiotoxic side effects. Nat Rev Clin Oncol 5, 324–335 (2008). https://doi.org/10.1038/ncponc1090

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