title: Trastuzumab in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: feasibility and preliminary efficacy.
abstract: OBJECTIVE
  We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer.
  
  
  METHODS
  Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks.
  
  
  RESULTS
  The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months.
  
  
  CONCLUSIONS
  DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation.
  
  
  BACKGROUND
  UMIN000005603.
authors.affiliation: Department of Gastroenterology and Oncology, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, 770-8503, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mitsui
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyamoto
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Fujino
authors.forename: Toshi
authors.initials: T
authors.lastname: Takaoka
authors.forename: Jinsei
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Miwako
authors.initials: M
authors.lastname: Kagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohnuma
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kubo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osuga
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sato
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shinich
authors.initials: S
authors.lastname: Katsuki
authors.forename: Toshinori
authors.initials: T
authors.lastname: Okuda
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nobuoka
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; 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; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D066246:ErbB Receptors; D000068878:Trastuzumab; D002945:Cisplatin