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A multicenter phase II study of TSU-68, an oral multiple tyrosine kinase inhibitor, in combination with docetaxel in metastatic breast cancer patients with anthracycline resistance

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Abstract

Background

TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor, and fibroblast growth factor receptor. This open-label, non-comparative, multicenter phase II study evaluated TSU-68 in combination with docetaxel in patients with metastatic breast cancer that had relapsed within 1 year despite prior treatment with an anthracycline-containing regimen.

Methods

TSU-68 was orally administered on days 1–21, and docetaxel was intravenously delivered on day 1. The regimen was repeated every 21 days. Primary endpoint was objective response rate according to the RECIST guidelines version 1.0.

Results

TSU-68 in combination with docetaxel produced objective responses in 21.1% and clinical benefits in 42.1% of the patients, respectively (1 complete response, 3 partial response, and 4 stable disease for at least 24 weeks, n = 19). Median time to progression was 148 days, and median overall survival was 579 days. The common adverse drug reactions were leukopenia, neutropenia, nail disorder, malaise, dysgeusia, alopecia, and edema.

Conclusions

TSU-68 in combination with docetaxel showed a promising antitumor response with manageable toxicity in patients with anthracycline-resistant metastatic breast cancer. Further studies are warranted in a different population of breast cancer or other solid cancers.

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Acknowledgments

We are grateful to Yutaka Ariyoshi, Yuh Satata, Tomohide Tamura, Kojiro Shimozuma, Seigo Nakamura, and Yuichi Watanabe for extramural review. We thank Junichi Yonezawa Toyomitsu Sato, Masahito Komuro, Kentaro Nagai, Hiroshi Nakayama, Yuji Takami, Itsumi Takaya, Akira Fukushima, Katsuo Ohwada, Kenzo Iizuka, and Kiyoshi Eshima for assistance in data collection and analysis.

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Authors and Affiliations

  1. Department of Breast Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masakazu Toi

  2. Department of Surgery, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Masakazu Toi

  3. Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama, Japan

    Toshiaki Saeki

  4. Department of Breast Oncology, National Hospital Organization Shikoku Cancer Centre, 160 Minamiumemoto-machi-ko, Matsuyama, Ehime, 791-0280, Japan

    Toshiaki Saeki & Kenjiro Aogi

  5. Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan

    Hiroji Iwata

  6. Division of Breast Oncology, Saitama Cancer Centre, 818 Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan

    Kenichi Inoue

  7. Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Yutaka Tokuda

  8. Department of Surgery, National Hospital Organization Nagoya Medical Center Hospital, 4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi, 460-0001, Japan

    Yasuyuki Sato

  9. Department of Medical Oncology, The Cancer Institute of Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Yoshinori Ito

  10. Department of Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, Hyogo, 660-8511, Japan

    Yuichi Takatsuka

  11. Division of Medical Oncology, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kohoku-ku, Yokohama, 222-0036, Japan

    Hitoshi Arioka

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  1. Masakazu Toi
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Correspondence to Masakazu Toi.

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Toi, M., Saeki, T., Iwata, H. et al. A multicenter phase II study of TSU-68, an oral multiple tyrosine kinase inhibitor, in combination with docetaxel in metastatic breast cancer patients with anthracycline resistance. Breast Cancer 21, 20–27 (2014). https://doi.org/10.1007/s12282-012-0344-3

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  • DOI: https://doi.org/10.1007/s12282-012-0344-3

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