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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

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 events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more 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.

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Correspondence to Hyun-Cheol Chung.

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S.-B. Kim and C. Yoo contributed equally to this work and should be considered as first co-authors.

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Kim, SB., Yoo, C., Ro, J. et al. 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. Invest New Drugs 32, 753–761 (2014). https://doi.org/10.1007/s10637-014-0093-6

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  • DOI: https://doi.org/10.1007/s10637-014-0093-6

Keywords

  • TSU-68
  • Breast cancer
  • Angiogenesis
  • Docetaxel