Single-Agent Topotecan as First-Line Chemotherapy in Women with Metastatic Breast Cancer: Final Results of Eastern Cooperative Oncology Group Trial E8193

The purpose of this multicenter phase II trial was to evaluate the clinical activity of topotecan as firstline chemotherapy in patients with metastatic breast cancer and previous exposure to adjuvant doxorubicin. Patients with measurable disease received a 72-hour continuous intravenous infusion of topotecan 1.3 mg/m 2 per day repeated every 21 days. The primary objective was to determine whether ≥ 4 responses were observed among 30 evaluable patients after 3 cycles of therapy using a 2-stage design (≥ 2 responses required in the first 20 evaluable patients). Duration of response, time to tumor progression, overall survival, and toxicity were also examined. Thirty-five patients altogether received 78 cycles of therapy (median, 3 cycles; range, 1–8 cycles). Two partial responses (6%; 95% confidence interval, 0.7%–19%) were observed among 30 evaluable patients (median age, 55 years; range, 34-76 years; median Eastern Cooperative Oncology Group performance status, 0; range, 0-2). Median time to progression and overall survival were 2.3 months and 18.7 months, respectively. Myelosuppression was the most common toxicity among 34 evaluable patients (grade 3/4 neutropenia and thrombocytopenia in 62% and 53%, respectively) with only 1 life-threatening event. Although tolerable, this dose and schedule of topotecan has limited activity in unselected patients with breast cancer even as first-line therapy. Identification of potential predictive markers of response and toxicity is encouraged before considering further studies of topotecan and camptothecin analogues in breast cancer.