Segar JM, Reed D, Stopeck A, et al. - Researchers undertook this single-arm phase 2 clinical trial, based on preclinical data, to test irinotecan (topoisomerase I inhibitor) combined with etoposide (topoisomerase II inhibitor) in patients (n = 31, median age was 54) with metastatic breast cancer (MBC) refractory to prior anthracycline, taxane, and capecitabine therapy. Treatment regimen administered was: oral etoposide at 50 mg/day on days 1–14 and intravenous irinotecan at 100 mg/m² on days 1 and 15. Every 28 days, treatment cycles were repeated. Most of the patients (64%) included had hormone receptor positive human epidermal growth factor receptor 2 negative MBC. Only modest clinical activity of irinotecan and etoposide and poor tolerability of this treatment regimen was evident in these patients. Given ease of administration and responses seen, a lower dose and/or different schedule could be assessed in further investigations.