title: Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group.
abstract: OBJECTIVE
  The synergic combination of oxaliplatin and capecitabine has demonstrated activity against various gastrointestinal cancers, including colon cancer. We therefore undertook this phase II study to test this first-line combination in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia.
  
  
  METHODS
  Forty-three patients with histologic or cytologic confirmation of the above malignancy were recruited. The cohort had Eastern Cooperative Oncology Group performance statuses of 0, 1 and 2 in 47%, 51%, and 2%, respectively. Median age was 61 years (range 32-80). All had adequate organ function. Initially, patients were prescribed 130 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice a day, on days 1-14 of a 21-day cycle. Four treatment-related deaths in the first 24 patients led to a reduction in capecitabine to 850 mg/m2 orally twice a day, days 1-14, for the remainder of the cohort.
  
  
  RESULTS
  The tumor response rate was 35% [95% confidence intervals (CI) 23% to 50%]. All responses were partial; seven of 24 occurred before the capecitabine dose reduction, and eight of 19 after. Median time to tumor progression was 4 months (95% CI 3.1-4.6), and median survival 6.4 months (95% CI 4.6-10). To date, there have been 36 deaths. Four were treatment-related (one infection, two myocardial infarctions, one respiratory failure), and all occurred before the capecitabine dose reduction. Notable grade 4 events from the entire cohort included diarrhea (two patients), vomiting (three), dyspnea (one), thrombosis (two) and anorexia (two). Grade 3 events included nausea (12 patients), diarrhea (12), fatigue (10), abdominal pain (seven), vomiting (six), dyspnea (six), hypokalemia (six), dehydration (five), hypokalemia (five) and infection (four).
  
  
  CONCLUSIONS
  Oxaliplatin and capecitabine in combination demonstrates activity in metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia. The lower dose (capecitabine 850 mg/m2 orally twice a day, days 1-14, and oxaliplatin 130 mg/m2 intravenously on day 1) yielded an acceptable toxicity profile and merits further study.
authors.affiliation: Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. Jatoi.aminah@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Jatoi
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
authors.forename: N R
authors.initials: NR
authors.lastname: Foster
authors.forename: D A
authors.initials: DA
authors.lastname: Nikcevich
authors.forename: S R
authors.initials: SR
authors.lastname: Alberts
authors.forename: J A
authors.initials: JA
authors.lastname: Knost
authors.forename: T R
authors.initials: TR
authors.lastname: Fitch
authors.forename: K M
authors.initials: KM
authors.lastname: Rowland
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002299:Cardia / Q000187:drug effects* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil