title: Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer.
abstract: OBJECTIVE
  The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer.
  
  
  METHODS
  We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses.
  
  
  RESULTS
  All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months.
  
  
  CONCLUSIONS
  The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.
authors.affiliation: Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610, Singapore.
authors.forename: Clarinda
authors.initials: C
authors.lastname: Chua
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Wei Peng
authors.initials: WP
authors.lastname: Yong
authors.forename: Whee Sze
authors.initials: WS
authors.lastname: Ong
authors.forename: Chee Kian
authors.initials: CK
authors.lastname: Tham
authors.forename: Matthew
authors.initials: M
authors.lastname: Ng
authors.forename: David W M
authors.initials: DW
authors.lastname: Tai
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.forename: Hwee Yong
authors.initials: HY
authors.lastname: Lim
authors.forename: Su-Pin
authors.initials: SP
authors.lastname: Choo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004338:Drug Combinations; D066246:ErbB Receptors / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D066246:ErbB Receptors; D000068878:Trastuzumab; D002945:Cisplatin