Phase II trial of topotecan in advanced breast cancer - A Cancer and Leukemia Group B study

The topoisomerase I inhibitor topotecan had demonstrated good antitumor act ivity in several murine tumor systems and in human clonogenic assays by 199 3. In that year, the Cancer and Leukemia Group B (CALGB) began a phase II t rial to determine its activity in patients with breast cancer who had previ ously received one course of chemotherapy for advanced breast cancer. Betwe en April 1993 and June 1994. 53 patients of performance status 0-2 entered the study, of whom 47 were eligible and 40 were evaluable. Topotecan was gi ven at a dose of 1.5 mg/m(2) over 30 minutes daily for 5 days every 21 days . In the absence of progression or withdrawal of consent, therapy was. cont inued indefinitely. The median age was 58 years (range 30-79). There were n o complete responses and fi,ur partial responses, resulting in an objective response rate of 10% (95% CI: 3-24%). Responses were noted in lymph nodes, liver, and skin. The median duration of response was 5 months. The median survival was 12 months. Life-threatening toxicities were almost exclusively hematologic, However, myelosuppression was not cumulative. It was conclude d that topotecan has only modest activity among women with advanced breast cancer who have previously received one course of chemotherapy. Given its m odest activity and predominant hematologic toxicity, it does not appear to be a promising drug for either single-agent or combination chemotherapy in the salvage setting of advanced breast cancer.