Anthracyclines and trastuzumab; getting to the heart of the matter: when getting to the heart is the matter

Excerpt

Despite expanding treatment options, anthracyclines remain among the most active chemotherapeutic agents for breast cancer. In HER2-positive metastatic breast cancer (MBC) the pivotal phase III study by Slamon et al. demonstrated that the addition of trastuzumab to chemotherapy improved the median time to disease progression from 4.6 to 7.4 months [1]. The addition of trastuzumab to anthracyclines (doxorubicin or epirubicin given once every 3 weeks) increased the rate of all grades of cardiac failure from 8% to 27% [2]. Following the publication of these data trastuzumab has not been routinely administered concurrently with anthracycline-based chemotherapy, and adjuvant studies have utilized a sequential approach. In order to “improve the therapeutic index of anthracycline/trastuzumab combinations” in MBC Gennari et al. designed a phase II study, published in the current issue of this journal, and discussed in this commentary. In this study patients with HER2-positive MBC were treated with epirubicin 90 mg/m² every 3 weeks in combination with so-called weekly “low-dose” trastuzumab (2 mg/kg loading dose then 1 mg/kg) [3]. …