title: Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: results of a randomised Phase 2 study.
abstract: BACKGROUND
  Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients.
  
  
  METHODS
  The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel+oxaliplatin (DOCOX)=docetaxel 60 mg/m(2) plus oxaliplatin 130 mg/m(2) on Day 1 of each 21-day cycle. Arm 2: docetaxel+oxaliplatin+cetuximab (DOCOX+C)=DOCOX with C 400mg/m(2) first dose then 250 mg/m(2) weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status.
  
  
  RESULTS
  One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX+C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings.
  
  
  CONCLUSIONS
  Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.
authors.affiliation: US Oncology Research, McKesson Specialty Health, The Woodlands, TX, USA. donald.richards@usoncology.com
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.forename: Darren M
authors.initials: DM
authors.lastname: Kocs
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Spira
authors.forename: A
authors.initials: A
authors.lastname: David McCollum
authors.forename: Sami
authors.initials: S
authors.lastname: Diab
authors.forename: Lanny I
authors.initials: LI
authors.lastname: Hecker
authors.forename: Allen
authors.initials: A
authors.lastname: Cohn
authors.forename: Feng
authors.initials: F
authors.lastname: Zhan
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D018631:ras Proteins / Q000235:genetics
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D043823:Taxoids; D000077150:Oxaliplatin; D000077143:Docetaxel; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab
keywords: Adenocarcinoma; Drug therapy; Gastroesophageal junction; KRAS