title: Vorinostat in combination with capecitabine plus cisplatin as a first-line chemotherapy for patients with metastatic or unresectable gastric cancer: phase II study and biomarker analysis.
abstract: BACKGROUND
  Vorinostat, a histone deacetylase (HDAC) inhibitor, was investigated in combination with capecitabine plus cisplatin (XP) as a first-line chemotherapy for patients with unresectable or metastatic gastric cancer (GC).
  
  
  METHODS
  Eligible patients received 400 mg vorinostat once daily on days 1-14, 1000 mg m(-2) capecitabine twice daily on days 1-14, and 60 mg m(-2) cisplatin on day 1 every 3 weeks. Plasma levels of acetyl-H3, HDAC2, and p21 were measured for correlative analysis. The primary end point was the 6-month progression-free survival (PFS) rate. Secondary end points included the response rate, PFS, overall survival (OS), and safety profile.
  
  
  RESULTS
  A total of 45 patients with HER2-negative GC were included in this study. The objective response rate was 42%. The median PFS was 5.9 months, and the 6-month PFS rate was 44.4%. The median OS was 12.7 months. Most common grade 3-4 toxicities were neutropenia (41%), fatigue (34%), anorexia (32%), thromboembolism (27%), stomatitis (14%), and thrombocytopenia (11%). High plasma acetyl-H3 and p21 levels were significantly associated with a poor OS (P=0.02 and P=0.03, respectively).
  
  
  CONCLUSIONS
  Vorinostat-XP is a feasible first-line chemotherapy for patients with advanced GC. However, this trial did not meet its primary end point, and more adverse events were observed in comparison with the historical data of flouropyrimidine-platinium doublet regimens.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Na
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Baek-Yeol
authors.initials: BY
authors.lastname: Ryoo
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Chae-Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000107:Acetylation; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000097:blood; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D056464:Histone Deacetylase 2 / Q000097:blood; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D006657:Histones / Q000097:blood; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009503:Neutropenia / Q000139:chemically induced; D011499:Protein Processing, Post-Translational; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013923:Thromboembolism / Q000139:chemically induced; D016896:Treatment Outcome; D000077337:Vorinostat
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D000077337:Vorinostat; D000069287:Capecitabine; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2; D002945:Cisplatin