4044 Background: RCT with 4 cycles (cy) FU/CDDP and 50 Gy (RTOG regimen) is the reference treatment (Tt) for patients (pts) with Inoperable EC, and is associated with 25% long-term survival.To improve these results, we assessed safety and activity of RCT using FU/FA/Ox in EC. METHODS pts with adenocarcinoma (AC), squamous cell (SC), adenosquamous carcinoma (ASC); no prior Tt; radiotherapy (RT) field < 30 cm high; primary tumor ≥5 cm high or metastases; age 18-75 yrs; PS ≤ 2. Tt: 3 RCT cy followed by 3 cy Folfox 4.RCT: Ox d1, FU bolus (b) + Continuous infusion (ci) + FA fixed dose 200 mg/m2 d1-2 q2 weeks (wks) with concurrent RT 50 Gy in 25 fractions/ 5 wks. 5 doses levels (mg/m2): Ox (50-75-85-100), FUb (300-400), FUci (400-600), then Folfox 4, 3 cy d1-2 q2 wks. First endpoint: Maximal Tolerated Dose (MTD) of Ox/FU + RT 50 Gy (dose level at which at least 3/3 or 3/6 pts experience dose limiting toxicity defined as G4 hematotoxicity or G3-4 non-hematotoxicity except esophagitis, dysphagia, nausea and vomiting). RESULTS 33 pts treated; 12LA/21m; 26M/7F; 10AC/4ASC/19SC; median age 58 (35-76); median cy 6 (1-10); 56 % pts completed therapy. MTD was observed at level 5 (mg/m2) Ox : 100 + FUb/ci: 400/600.Recommended doses are (mg/m2) Ox: 85 + FUb/ci: 400/600 (Folfox 4).Efficacy in 28 evaluable pts: ORR = 61 % (3CR, 14PR). Median TTP and overall survival (months): 5 [95% CI : 3- 6] and 9 [95% CI : 5- 13]. CONCLUSIONS In EC Ox/FU/FA + RT 50 Gy is safe and active; a randomised phase II/III study comparing Folfox 4 + RT 50 Gy versus RTOG regimen is starting. No significant financial relationships to disclose.