353 Adjuvant Capecitabine and Cisplatin Versus Surgery Alone in Patients With Esophageal Squamous Cell Carcinoma: Multicenter Randomized Phase 3 Trial

Abstract

There is limited evidence for effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma. We conducted a multi-center randomized controlled trial to assess whether adjuvant Capecitabine and Cisplatin improve survival compared with surgery only among patients with resectable esophageal squamous cell carcinoma. Methods This is a multicenter randomized controlled trials conducted at five hospitals in Korea from Mar 2005 to Dec 2018. Patients were eligible if they underwent curative resection for esophageal squamous cell carcinoma and diagnosed with pathologic T2–3 or N1 stage, according to 6th edition of TNM cancer staging system. Patients who were diagnosed with cervical esophageal cancer, had previous history of cancer, or received neoadjuvant therapy were excluded. Intervention group received 4 cycles of adjuvant chemotherapy (Capecitabine 1,000 mg/m2 b.i.d for 14 days and intravenous Cisplatin 75 mg/m2 at Day1, every 3 weeks). The primary endpoint was disease free survival. Results 136 patients were randomly assigned to adjuvant chemotherapy group (n = 68) or surgery alone group (n = 68). Seven patients who rejected chemotherapy after randomization were excluded from the final analysis. The cumulative incidence of recurrence within 18 months after surgery was significantly lower in the adjuvant chemotherapy group compared to the surgery alone group (Hazard Ratio (HR), 0.45; 95% Confidence Interval (CI), 0.22–0.91). After long-term follow-up (median 3.3 years, maximum 14 years), disease free survival and overall survival were not different between two groups. (HR, 0.77; 95% CI, 0.49–1.18 and HR, 0.85; 95% CI, 0.55–1.34, respectively.) Conclusion Adjuvant chemotherapy after curative resection in patients with esophageal squamous cell carcinoma reduced early recurrence but this does not extend to long-term disease free and overall survival due to limited sample size. Additional randomized controlled trials with larger sample would be necessary to confirm the effectiveness of adjuvant chemotherapy in esophageal squamous cell carcinoma.