title: A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker.
abstract: OBJECTIVE
  The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer.
  
  
  METHODS
  Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry.
  
  
  RESULTS
  A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%.
  
  
  CONCLUSIONS
  Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.
authors: Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan.
authors: Masahiro
authors: M
authors: Hirakawa
authors: Yasushi
authors: Y
authors: Sato
authors: Hiroyuki
authors: H
authors: Ohnuma
authors: Tetsuji
authors: T
authors: Takayama
authors: Tamotsu
authors: T
authors: Sagawa
authors: Takayuki
authors: T
authors: Nobuoka
authors: Keisuke
authors: K
authors: Harada
authors: Hiroshi
authors: H
authors: Miyamoto
authors: Yasuhiro
authors: Y
authors: Sato
authors: Yasuo
authors: Y
authors: Takahashi
authors: Shinich
authors: S
authors: Katsuki
authors: Michiaki
authors: M
authors: Hirayama
authors: Minoru
authors: M
authors: Takahashi
authors: Michihiro
authors: M
authors: Ono
authors: Masahiro
authors: M
authors: Maeda
authors: Kohichi
authors: K
authors: Takada
authors: Tsuyoshi
authors: T
authors: Hayashi
authors: Tsutomu
authors: T
authors: Sato
authors: Koji
authors: K
authors: Miyanishi
authors: Rishu
authors: R
authors: Takimoto
authors: Masayoshi
authors: M
authors: Kobune
authors: Koichi
authors: K
authors: Hirata
authors: Junji
authors: J
authors: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D019160:Endosonography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin