Phase II trial of dolastatin-10 in patients with advanced breast cancer
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Purpose: Phase II multicenter cooperative group study investigated the efficacy and toxicity of the novel anti-microtubule agent dolastatin-10 in patients with advanced breast cancer.
Patient and methods: Twenty-one patients with measurable metastatic breast cancer were treated with dolastatin-10 at a dose of 400 mcg/m2 by intravenous bolus once every 3 weeks. Patients must have received a total of 1 or 2 prior chemotherapy regimens and have an Eastern Cooperative Oncology Group performance status of 0–2. Patients received this treatment as either a first (n = 11) or second-line (n = 10) chemotherapy for metastatic disease. Eighteen patients (86%) had received a prior anthracycline. The National Cancer Institute provided the dolastatin-10.
Results: One out of 21 patients (5%; 95% CI: 0–24%) achieved a partial remission for a duration of 113 days. Four patients maintained stable disease for a median of 87 days. A total of 58 courses of dolastatin-10 were administered. Patients received a median of two cycles of dolastatin-10. Hematologic toxicity was moderate, with 8 patients developing grade 4 neutropenia, and 5 with grade 3 neutropenia; one grade 3 febrile neutropenia was observed. These episodes of grade 3 and 4 neutropenia were experienced on 36% of the treatment cycles. Non-hematologic toxicity was uncommon.
Conclusion: While the toxicity profile of dolastatin-10 was acceptable, it had minimal activity in this advanced breast cancer study. We are not pursuing further clinical trials of this agent in the setting of advanced breast cancer.
Key wordsmetastatic breast cancer dolastatin-10 investigational drug anti-tubulin agent
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