title: A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival.
abstract: BACKGROUND
  We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome.
  
  
  METHODS
  Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.
  
  
  RESULTS
  From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes.
  
  
  CONCLUSIONS
  Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Young-Woo
authors: YW
authors: Kim
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Mi-Jung
authors: MJ
authors: Kim
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Keun Won
authors: KW
authors: Ryu
authors: Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.|Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Hyeong-Seok
authors: HS
authors: Lim
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Jun Ho
authors: JH
authors: Lee
authors: Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Sun-Young
authors: SY
authors: Kong
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Jong Seok
authors: JS
authors: Lee
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Il Ju
authors: IJ
authors: Choi
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Chan Gyoo
authors: CG
authors: Kim
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Jong Yeul
authors: JY
authors: Lee
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Soo-Jeong
authors: SJ
authors: Cho
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Myeong-Cherl
authors: MC
authors: Kook
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Young-Iee
authors: YI
authors: Park
authors: Department of Nuclear Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.
authors: Seok-Ki
authors: SK
authors: Kim
authors: Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea. sukryun73@hanmail.net.|Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea. sukryun73@hanmail.net.
authors: Sook Ryun
authors: SR
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004338:Drug Combinations; D005260:Female; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D019990:Perioperative Care; D010597:Pharmacogenetics; D011182:Postoperative Care; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6
keywords: CYP2A6 genotype; Docetaxel; Gastric cancer; Perioperative chemotherapy; S-1