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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



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.


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.


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.


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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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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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).

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  • Receptor tyrosine kinase inhibitor
  • Phase II study
  • Anthracycline-resistant breast cancer