Fig. 1

Study strategy and design. Patients previously received three or fewer chemotherapeutic regimens (not including adjuvant therapy) with MBC were enrolled. Both combination therapy and monotherapy were carried out in two stages. In the first stage of combination therapy, three doses of utidelone (30, 35, and 40 mg/m²/day) plus capecitabine (2000 mg/m²/day) were tested, with each dose group recruiting 3–5 patients of total 12 patients. Based on the efficacy and toxic effects of the combined agents, 30 mg/m²/day dosing regimen was selected, which demonstrated better safety profile with promising efficacy, as the dose for the second stage that recruited 21 patients. For the monotherapy, compare two different dosing regimens in the first stage: (1) 170 mg/m² iv, once every 21 days; (2) 40 mg/m² iv, once daily for 5 days every 21 days. Patients were randomized into the two different regimens, and 15 patients for each group were enrolled. Based on the efficacy and safety of the first stage, 40 mg/m²/day dosing regimen was chosen for the second stage to continue recruitment until target patient number reached 55. Efficacy evaluation was carried out once every 2 cycles, and the primary endpoint ORR was assessed