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Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer

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Summary

The primary objective of study is to evaluate cardiac safety of trastuzumab in combination with epirubicin and docetaxel. HER2-overexpressing metastatic breast cancer patients were enrolled in a two-stage, multicenter phase II trial with weekly trastuzumab (4 and then 2 mg/kg) with epirubicin and docetaxel (either 75 mg/m2) on day 1 every 3 weeks. After eight courses of chemotherapy, trastuzumab was continued as a single agent. To assess cardiotoxicity, patients were evaluated for left ventricular ejection fraction (LVEF) at baseline, every two cycles during chemotherapy and trastuzumab, and every 3 months during trastuzumab alone. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure (CHF) and/or an absolute decrease in LVEF of ≥20 units or a decline to ≤45%. In the first stage of the study, three episodes of cardiotoxicity were observed (two asymptomatic declines of LVEF and one CHF) in 29 patients, and recruitment continued. During follow-up of patients who continued trastuzumab after chemotherapy, seven further cardiologic events occurred (three asymptomatic decline of LVEF and four CHF). Therefore, recruitment was interrupted after the 45th patient. The majority of cardiac events occurred late during trastuzumab alone, half were asymptomatic and all cases of CHF were resolved using cardiac therapy. Complete and partial responses were 20 and 47%, respectively, and the median time to progression was 15.7 months (95% CI, 11.6–19.0 months). In light of the cardiotoxicity experienced during this study, we currently recommend that this combination be used only in controlled clinical trials under vigilant cardiac monitoring.

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Acknowledgments

The authors thank Dr. Giovanna Cavazzini and Dr. Marco Danova for their participation to the study and for their contribution to article preparation.

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Authors and Affiliations

  1. Division of Medical Oncology, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, I-16132, Genova, Italy

    M. Venturini, C. Bighin & L. Del Mastro

  2. Ospedale Civile, Padova, Italy

    S. Monfardini & O. Nicoletto

  3. Ospedale Bellaria, Bologna, Italy

    F. Cappuzzo

  4. Azienda Ospedaliera USL 1, Sassari, Italy

    N. Olmeo

  5. Ospedale S. Anna, Torino, Italy

    A. Durando

  6. Policlinico Città di Udine, Udine, Italy

    F. Puglisi

  7. Roche S.p.A, Milano, Italy

    A. Lambiase

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  1. M. Venturini
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Correspondence to M. Venturini.

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Address for offprints and correspondence: Marco Venturini, Division of Medical Oncology, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, I-16132 Genova, Italy; Tel.: +39-10-560-0898; Fax: +39-10-560-0850; E-mail: marco.venturini@istge.it

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Venturini, M., Bighin, C., Monfardini, S. et al. Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer. Breast Cancer Res Treat 95, 45–53 (2006). https://doi.org/10.1007/s10549-005-9030-x

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