F-048A PHASE III CLINICAL TRIAL OF NEOADJUVANT CHEMORADIOTHERAPY FOLLOWED BY SURGERY VERSUS SURGERY ALONE FOR LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE OESOPHAGUS (NEOCRTEC5010)

Abstract

Objectives: Surgery is the main treatment of oesophageal squamous cell carcinoma (ESCC), but the prognosis of patients with locally advanced ESCC is rather poor. We are to carry out a phase III clinical trial to investigate the effect of preoperative chemoradiotherapy followed by surgery for the overall survival of patients with locally advanced ESCC. Methods: According to 6th Edition AJCC Cancer Staging, patients with IIB‐III staged ESCC are randomly allocated to either preoperative chemoradiotherapy followed by surgery (arm A), or surgery alone (arm B). In the arm A, Chemotherapy and radiotherapy are performed concurrently. Patients received 2 cycles of vinorelbine and cisplatin. Vinorelbine at 25 mg/m2 per day is administered in bolus infusion on day 1, day 8, day 22 and day 29. Cisplatin at 75 mg/m2 is administered by intravenously infusion on day 1 and day 22 (or 25 mg/m2 days 1 to 4 and 22 to 25). A total radiotherapy dose of 40 Gy is delivered in 20 daily fractions of 2.0 Gy each (given 5 days/week for 4 weeks). McKeown oesophagectomy or Ivor Lewis oesophagectomy will be performed 4‐6 weeks after chemoradiotherapy. Primary outcomes are 3‐and 5‐year overall survival. Results: From July 2007 to December 2014, 451 eligible patients were randomly assigned in 8 cooperative cancer centres (224 cases in arm A, and 227 cases in arm B). In arm A, 185 cases continued to undergo surgery after chemoradiotherapy. The rate of R0 resection was 98.4% (182/185) in arm A vs 91.2% (207/227) in arm B (P=0.002). A pathological complete response was achieved in 80 of 185 patients (43.2%) who underwent resection in the arm A. The overall survival at 3 years in arm A was significantly higher than arm B (69.6% vs 62.4%; HR 0.71 [95% CI 0.52‐0.98]; log‐rank P=0.035). Conclusions: Neoadjuvant chemoradiotherapy plus surgery improved survival among patients with locally advanced oesophageal squamous cell carcinoma.