Preoperative chemotherapy in patients with resectable esophageal carcinoma: a single center Phase II study

Objective: The role of preoperative chemotherapy in squamous cell esophageal carcinoma remains controversial. A prospective trial was initiated to investigate whether preoperative chemotherapy followed by surgery results in increased progression-free survival in patients with resectable thoracic esophageal carcinoma. Methods: Patients with Stage IIb-IIIa/b resectable esophageal carcinoma were eligible for the study. They received two cycles of FLEP regimen chemotherapy (cisplatin, etoposide, leucovorine, 5-fluorouracil) followed by transthoracic extended 2-or 3-field esophagectomy. Two-year progression-free survival was the primary endpoint. To evaluate the potential benefit of the dual-modality approach we compared these results with the outcome of patients who were treated in our center in the same period of time and were non-randomly allocated to surgery alone. Results: From 2001 to 2008, 63 patients were included in the study (bimodality group) and 58 patients into the surgery-alone group. Median follow-up was 68 (range, 4-123) months. Squamous cell carcinoma had 93% patients. Two-year progression-free survival for all patients was 45.3 and 30.7% (hazard ratio 0.71, 95% confidence interval 0.46-1.08) and median overall survival was 26.5 months and 18.0 months (hazard ratio 0.67, 95% confidence interval 0.41-1.01) in bimodality-and surgery-alone groups, respectively. Patients who underwent R0-resection after bimodality treatment had significantly better overall survival (40.9 months) than after surgery alone (19.0 months, hazard ratio 0.51, 95% confidence interval 0.30-0.81). Conclusions: Two cycles of preoperative chemotherapy did not improve progression-free survival of patients with resectable thoracic esophageal carcinoma in intent-to-treat population. However, significantly better results of bimodality approach was seen in R0-resected patients which warrants further trials with more effective chemotherapy combinations.