Perioperative versus Preoperative Chemotherapy with Surgery in Patients with Resectable Squamous Cell Carcinoma of Esophagus: A Phase III Randomized Trial.

BACKGROUND: Perioperative chemotherapy for resectable squamous cell carcinoma of esophagus remains elusive. Thus, we assessed whether a perioperative regimen of paclitaxel, cisplatin, and 5- fluorouracil (PCF) improved outcomes among patients with curable squamous cell carcinoma of esophagus comparing with preoperative chemotherapy alone. METHODS: Overall, 346 patients with resectable squamous cell carcinoma of esophagus were randomly assigned to receive surgery plus perioperative chemotherapy (175, arm A) or preoperative chemotherapy (171, arm B). Both arms received two preoperative cycles of PCF: intravenous paclitaxel (100 mg per square meter of body surface area) and cisplatin (60 mg per square meter of body surface area) on day 1, and a continuous intravenous infusion of 5- fluorouracil (700 mg per square meter of body surface area per day) for 5 days. Arm A received two added postoperative cycles of PCF. The primary end point was relapse-free survival, and the secondary end point was overall survival. RESULTS: Compared with preoperative chemotherapy group, perioperative chemotherapy group had a greater likelihood of 5-year relapse-free survival (hazard ratio for relapse, 0.62; 95% confidence interval, 0.49-0.73; 31% versus 17%, p < 0.001) and of 5-year overall survival (hazard ratio for death, 0.79; 95% confidence interval, 0.59-0.95; 38% versus 22%, p < 0.001). A pathologic complete response rate was achieved in 77 of 320 patients (24.1%) who underwent resection after chemotherapy. The increased PCF-related toxic events were not detected with the addition of two postoperative cycles of PCF. CONCLUSION: In patients with operable esophageal squamous cell carcinoma, perioperative regimen of PCF can significantly improve 5-year relapse-free and overall survival comparing with preoperative chemotherapy alone. (The trial has been registered at ClinicalTrials.gov, number NCT01225523.).