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目的 评价术前放化疗并手术治疗局部晚期食管癌的安全性与近期疗效.方法 开展多中心前瞻性随机对照临床研究,入组ⅡB、Ⅲ期胸段食管鳞癌患者,随机分组为试验组(术前放化疗组)与对照组(单纯手术组).试验组术前放化疗方案:去甲长春花碱联合顺铂化疗,同期采用常规分割放疗2.0 Gy/d,每周5d,总量40 Gy.放化疗结束4～6周后,施行三切口食管癌切除术.对照组患者直接接受手术.主要终点观测指标是总生存.结果 2007年7月1日至2011年6月1日,7个试验中心共入组患者123例,随机分组为试验组54例,对照组69例.试验组术前放化疗的临床有效率90.7％,49例进一步接受手术.试验组的RO切除率高于对照组(96.0％比85.5％,P=0.015),病理完全缓解率为29.6％.术前放化疗引起的3度以上急性毒性反应最常见是白细胞减少,达33例(61.1％),食管炎与呕吐也比较常见,多为1～2度,无术前放化疗的毒副反应导致无法手术或死亡.试验组与对照组的手术时间、术中出血量、胸管留置时间、术后住院时间差异无统计学意义.主要术后并发症,包括心功能不全、吻合口漏、声嘶、肺部感染发生率的发生率相似,两组均无患者出现围术期死亡.试验组与对照组的1、2年生存率差异无统计学意义(85.6％/75.5％比79.1％/66.1％,P=0.207),试验组的1、2年无瘤生存率稍高于对照组(86.6％/83.2％比70.9％/61.8％,P=0.075).结论 中期分析显示,术前放化疗并手术可取得确切的临床有效率和较高的完全病理缓解率,明显降低食管癌的分期,提高了RO切除率,并且安全性较高,有延长生存与无瘤生存的趋势.

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.