Single-agent topotecan as first-line chemotherapy in women with metastatic breast cancer: Final results of Eastern Cooperative Oncology Group trial E8193

Purpose: The purpose of this multicenter phase II trial was to evaluate the clinical activity of topotecan as first-line chemotherapy in patients with metastatic breast cancer and previous exposure to adjuvant doxorubicin. Patients and methods: Patients with measurable disease received a 72-hour continuous intravenous infusion of topotecan 1.3 mg/m² 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). Results: 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. Conclusion: 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.