title: A phase II trial of induction epirubicin, oxaliplatin, and fluorouracil, followed by surgery and postoperative concurrent cisplatin and fluorouracil chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction.
abstract: BACKGROUND
  Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy.
  
  
  METHODS
  Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy.
  
  
  RESULTS
  Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control.
  
  
  CONCLUSIONS
  Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.
authors.affiliation: *Cleveland Clinic, Taussig Cancer Institute, Solid Tumor Oncology, Cleveland, OH; †Cleveland Clinic, Taussig Cancer Institute, Radiation Oncology, Cleveland, OH; ‡Cleveland Clinic, Heart and Vascular Institute, Thoracic and Cardiovascular Surgery, Cleveland, OH; §Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA; and ‖Cleveland Clinic, Quantitative Health Sciences, Cleveland, OH.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McNamara
authors.forename: David J
authors.initials: DJ
authors.lastname: Adelstein
authors.forename: Joanna W
authors.initials: JW
authors.lastname: Bodmann
authors.forename: John F
authors.initials: JF
authors.lastname: Greskovich
authors.forename: Denise I
authors.initials: DI
authors.lastname: Ives
authors.forename: David P
authors.initials: DP
authors.lastname: Mason
authors.forename: Sudish C
authors.initials: SC
authors.lastname: Murthy
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rice
authors.forename: Jerrold P
authors.initials: JP
authors.lastname: Saxton
authors.forename: Davendra
authors.initials: D
authors.lastname: Sohal
authors.forename: Kevin
authors.initials: K
authors.lastname: Stephans
authors.forename: Cristina P
authors.initials: CP
authors.lastname: Rodriguez
authors.forename: Gregory M M
authors.initials: GM
authors.lastname: Videtic
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Rybicki
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059186:Chemoradiotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000473:pathology / Q000628:therapy*; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil