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Evaluation of Epothilone B Analog in Advanced Soft Tissue Sarcoma: A Phase II Study of the Phase II Consortium

From the Mayo Clinic College of Medicine, Rochester, MN; Mayo Clinic, Division of Oncology, Jacksonville, FL; Mayo Clinic, Department of Hematology/Oncology, Scottsdale, AZ; University of Wisconsin Comprehensive Cancer Center, Madison, WI; Howard University, Washington, DC; Washington University School of Medicine, St Louis, MO; Karmanos Cancer Institute at Wayne State University, Detroit, MI; and The Johns Hopkins Oncology Center, Baltimore, MD

Address reprint requests to Scott H. Okuno, MD, Mayo Clinic College of Medicine, 200 First St, Southwest, Medical Oncology, Rochester, MN 55905; e-mail: okuno.scott{at}mayo.edu

PURPOSE: Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease.

PATIENTS AND METHODS: Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m² intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later.

RESULTS: Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%).

CONCLUSION: BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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