A multi-centered randomized controlled study of neo-adjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of esophagus: an interim analysis

Objective To evaluate the safety and validity of neo-adjuvant chemoradiotherapy followed by surgery for locally advanced esophageal carcinoma.Methods Patients with Ⅱ B,Ⅲ staged squamous cell carcinoma of thoracic esophagus were randomly allocated to either preoperative chemoradiotherapy followed by surgery ( arm A ) or surgery alone ( arm B ).In arm A,chemotherapy and radiotherapy were performed concurrently.Patients received two cycles of vinorelbine and cisplatin.Vinorelbine at 25 mg/m2 per day was administered as a bolus infusion at dl,d8,d22 and d29.Cisplatin at 75 mg/m2 was administered by an intravenous infusion at dl and d22( or 25 mg/m2 days 1 - 4 and 22 - 25 ).A total radiotherapeutic dose of 40 Gy was delivered in 20 daily fractions of 2.0 Gy each (5 d/wk for 4 weeks ).Three-incisioned esophagectomy was performed at Weeks 4 - 6 after chemoradiotherapy.Primary outcome was overall survival time.An interim analysis was performed in June 2011.Results From July 2007 to June 2011,123 eligible patients were randomly assigned at 7 cooperative cancer centers (54 cases in arm A vs 69 cases in arm B).In arm A,the clinical response rate of chemoradiotherapy was 90.7％.All patients finished the preoperative chemoradiotherapy. Forty-nine cases continued to receive esophagectomy.The pathological complete response rate was 29.6％.The rate of RO resection in arm A was significant higher than that in arm B (96.0％ vs 85.5％,P =0.015 ).The most common grade 3/4 toxicity of chemoradiotherapy was leukopenia occurring in 33 cases (61.l％ ).Vomiting and esophagitis were usually of Grade 1/2.No patient died or abandoned surgery because of chemoradiation toxicity.Between arms A and B,operative duration,blood loss,duration of chest tube drainage and length of postsurgical hospital stay were similar.The incidences of postoperative heart failure (2.0％ vs 1.4％,P =1.000),anastomotic leakage(8.2％ vs 11.6％,P =0.759)and hoarseness(6.1％ vs 4.3％,P =0.691 )were not significantly different.The incidence of pulmonary infection in arm A was slightly higher than that in arm B (8.2％ vs 1.4％,P=0.094).No perioperative deaths occurred in either group.There were no significant differences in overall survivals at 1,2 years between arms A and B(85.6％/75.5％ vs 79.1％/66.1％,P =0.207).The disease-free survivals at 1,2 years in arm A were slightly higher than in arm B (86.6％/83.2％ vs 70.9％/61.8％,P =0.075 ).Conclusion Neo-adjuvant chemoradiation followed by surgery may achieve a high clinical response rate and pathologic complete tumor regression rate.It significantly increases the RO resection rate and downstage the esophageal cancer patients.But its ultimate efficacy awaits further follow-up studies. Key words: Esophageal neoplasms ;  Radiotherapy ;  Drug therapy ;  Surgical procedures,operative