Sagopilone is a novel, fully synthetic epothilone that has shown promising preclinical activity in a range of tumor models, including platinum-resistant ovarian cancer and metastatic breast cancer (MBC). This open-label, multicenter, Phase II study investigated the efficacy, safety, and tolerability of sagopilone administered to patients with MBC. Women with MBC whose previous chemotherapy regimen included a taxane and an anthracycline received sagopilone 16 or 22 mg/m(2) as a 3-h intravenous infusion every 21 days. Efficacy (using modified Response Evaluation Criteria in Solid Tumors), safety, and tolerability were assessed in this population. A total of 65 patients received sagopilone at either 16 mg/m(2) (N = 39) or 22 mg/m(2) (N = 26). Patients received a median of two cycles of sagopilone. Among the 65 patients who were evaluable for efficacy, there were three confirmed tumor responses over both treatment arms; however, the primary target of the study was not reached. The main treatment-related adverse events were sensory neuropathy (81.5%) and fatigue (44.6%). There were no deaths related to the study drug. Sagopilone was moderately tolerated in both treatment arms and showed limited activity in heavily pre-treated patients with MBC.