title: Phase I study of S-1 in combination with trastuzumab for HER2-positive metastatic breast cancer.
abstract: BACKGROUND
  As there are no reports of S-1 in combination with trastuzumab in clinical settings, we evaluated the safety and efficacy of S-1 in combination with trastuzumab for human epidermal-growth factor receptor (HER2)-positive metastatic breast cancer (MBC) and determined the recommended dose (RD).
  
  
  METHODS
  Patients with HER2-positive MBC received trastuzumab (a fixed initial dose of 4 mg/kg/day, then 2 mg/kg every week) plus S-1 (4 weeks followed by a 2-week rest) every 42 days. The dosage of S-1 was set of three levels (1: 80 mg/m², 2: 65 mg/m², 3: 50 mg/m²). The purposes of this study were the determination of the RD and safety. Dose-limiting toxicity (DLT) data were continually monitored to assess S-1 dose decreases.
  
  
  RESULTS
  Twelve patients were treated at level 1. Because no patients experienced DLT, the RD of S-1 plus trastuzumab therapy was 80 mg/m² S-1 and 4 mg/kg followed by 2 mg/kg trastuzumab. The overall response rate and disease control rate were 33.3% and 83.3%, respectively.
  
  
  CONCLUSIONS
  S-1 plus trastuzumab could be safely and effectively used for the treatment of HER2-positive MBC. The RD for a phase II study of this regimen was determined to be 80 mg/m² S-1 and 2 mg/kg trastuzumab every week (loading dose, 4 mg/kg).
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita City, Osaka 565-0871, Japan. taqnakayama@gmail.com
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takashima
authors.forename: Shunji
authors.initials: S
authors.lastname: Kamigaki
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Yoshidome
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Taguchi
authors.forename: Junichi
authors.initials: J
authors.lastname: Sakamoto
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000068878:Trastuzumab