title: 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.
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.
authors.affiliation: Department of Breast Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan, toi@kuhp.kyoto-u.ac.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Arioka
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000077143:Docetaxel; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D000078183:Oxindoles; D011422:Propionates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D018943:Anthracyclines; D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D043823:Taxoids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; C412603:orantinib