[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 IIB, 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/m(2) per day was administered as a bolus infusion at d1, d8, d22 and d29. Cisplatin at 75 mg/m(2) was administered by an intravenous infusion at d1 and d22 (or 25 mg/m(2) 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 R0 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 (61.1%). 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).


CONCLUSIONS
Neo-adjuvant chemoradiation followed by surgery may achieve a high clinical response rate and pathologic complete tumor regression rate. It significantly increases the R0 resection rate and down stage the esophageal cancer patients. But its ultimate efficacy awaits further follow-up studies.
Department of Thoracic Oncology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
Hong
H
YANG
Jian-hua
JH
FU
Meng-zhong
MZ
LIU
Wen-tao
WT
FANG
Jia-ming
JM
WANG
Yu-ping
YP
CHEN
Zhi-jian
ZJ
CHEN
Jia-qing
JQ
XIANG
Huan-jun
HJ
YANG
Wei-min
WM
MAO
Xiao
X
ZHENG
Cheng-chu
CC
ZHU
Min
M
KONG
Yong-tao
YT
HAN
Tao
T
LI
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000601:surgery / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000601:surgery / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies