title: A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy.
abstract: BACKGROUND
  The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes.
  
  
  METHODS
  Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis.
  
  
  RESULTS
  Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis.
  
  
  CONCLUSIONS
  The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer.
authors.affiliation: Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hei-Cheul
authors.initials: HC
authors.lastname: Jeung
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Chong Kun
authors.initials: CK
authors.lastname: Im
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Shin
authors.forename: Joong Bae
authors.initials: JB
authors.lastname: Ahn
authors.forename: Woo Ick
authors.initials: WI
authors.lastname: Yang
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Roh
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Noh
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000378:metabolism*; D010094:Oxonic Acid / Q000008:administration & dosage*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D015676:Osteonectin; D043823:Taxoids; C079198:S 1 (combination); D005641:Tegafur; D000077143:Docetaxel; D010094:Oxonic Acid; D002945:Cisplatin