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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

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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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Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Sung-Bae Kim, Changhoon Yoo, Jin-Hee Ahn & Kyung Hae Jung

  2. Center for Breast Cancer, National Cancer Center, Goyang, South Korea

    Jungsil Ro

  3. Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

    Seock-Ah Im

  4. Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Young-Hyuck Im

  5. Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea

    Jee Hyun Kim

  6. Division of Hematology/Oncology, Department of Medicine, Keimyung University Dongsan Hospital, Daegu, South Korea

    Hong Suk Song

  7. Department of Hematology and Oncology, Ajou University School of Medicine, Suwon, South Korea

    Seok Yun Kang

  8. Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea

    Hee Sook Park

  9. Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea

    Hyun-Cheol Chung

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  1. Sung-Bae Kim
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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

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