Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: Randomized phase Ⅱ multicenter trial

Abstract

Summary The novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1–21 plus docetaxel 60 mg/m2 on day 1 every 3 weeks, or docetaxel 60 mg/m2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI]=5.4–12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI=4.0–13.7 months) in the docetaxel-alone group (hazard ratio [HR]=1.0; 95 % CI=0.6– 1.8; p=0.95). There were no significant differences in the overall response rates and overall survival between groups (p=0.29 and p=0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR=0.3; 95%CI=0.1– 0.8; p=0.02). The most frequent adverse eventswere neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity wasmore frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup. Keywords TSU-68 . Breast cancer . Angiogenesis . Docetaxel