Background: Chemoradiotherapy (CRT) for locally advanced cardia and esophageal cancer is based on 5-FU combined with cisplatin, which could be favourably replaced by oxaliplatin (Ox). Cetuximab (C) has demonstrated synergism with both radiotherapy (RT) and platinum-based chemotherapy. ERaFOX trial was evaluating the safety and efficacy of the addition of C to CRT with FOLFOX. Methods: Main inclusion criteria were: stage III squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction; WHO PS 0-1; age 18-80 years; weight loss <15% in the last 6 months. Patients (pts) received 2 cycles of FOLFOX induction therapy (Ox 85 mg/m²/d1, folinic acid 400 mg/m²/d1, 5-FU 2,400 mg/m²/d1-2, q2w) plus C (first infusion 400 mg/m² then 250 mg/m², q1w), then RT 50.4 Gy (1.8Gy/d x 28 fractions) with FOLFOX plus C (same doses, except 5-FU 1,800mg/m²/d1-2). Tumor evaluation was performed at the end of CRT (RECIST and endoscopic ultrasonography). The primary endpoint was overall response rate (ORR), with a 50.0% threshold for efficacy (Simon Minimax two-stage design). Results: From Nov 2007 to Feb 2010, 80 pts were enrolled in 12 centers. The characteristics of the 79 eligible pts were (1 ineligible pt for stage IV disease): male/female 60/19, median age 63 (23-79), PS 0/1/ND 47/31/1, squamous/adenocarcinoma/undifferentiated 53/25/1; esophagus/cardia 74/5; median daily caloric intake 1720 Kcal (550-3160). 74 pts were treated by CRT (5 pts experienced anaphylaxis during the first cetuximab infusion). ORR (ITT) was achieved in 61 pts (77.2%; 95% CI 67.9-86.5). After a median follow-up of 19.4 months, median PFS/OS were 13.8/21.6 months. Nineteen (24.0%) pts experienced primitive resection. Pathological CR rate will be presented at the meeting. Most frequent grade 3-4 toxicities were: neutropenia (28.4%), dysphagia-esophagitis (13.5%), rash (10.8%) and allergy (8.9%). One toxic death (1.3%) occurred after CRT related to esophagitis with GI bleeding. Conclusions: Threshold for efficacy was reached with an ORR of 77.2%. Chemoradiotherapy with FOLFOX plus cetuximab should be compared to the same strategy without cetuximab in pts with locally advanced cardia or esophageal cancer.