Adjuvant chemotherapy with uracil-tegafur (UFT) for serosa negative advanced gastric cancer: Results of a randomized trial by national surgical adjuvant study of gastric cancer
4021 Background: To evaluate the survival benefit of adjuvant chemotherapy with UFT after curative resection in AGC patients (pts) with t2 and n1–2, a multi-center phase III clinical trial was conducted by 31 participating centers in Japan. Methods: Eligibility included pts with curative gastrectomy with D2 or greater lymph node dissection also with t2 and n1–2 AGC; PS:0–2; no prior chemotherapy. Patients were randomized in a 1:1 ratio to adjuvant chemotherapy or surgery alone. The treatment arm consisted of oral UFT 360mg/m2 (400–600mg/body)/day 6 weeks after surgery for the following 16 months. The primary endpoint was overall survival. Relapse-free survival and the site of recurrence were secondary endpoints. Assuming 244 eligible pts in each arm, the study had 0.8 power to detect 8.8% difference in 5-year survival rate. However this study was closed at an accrual of 190 pts because of slow recruitment and necessity to start adjuvant trial with more promising anticancer drug, S-1. All p-values reported are two-sided. Results: Between 06/1997 to 03/2001, 188 pts were randomized to chemotherapy arm (93 pts) or surgery alone arm (95 pts) excluding two pts with early gastric cancer. There was no treatment-related death. Although grade 3 adverse events were observed in 33% of pts (neutropenia (13.3%), increase in serum total bilirubin (9.0%), etc), grade 4 adverse effects (diarrhea) appeared in only one patient (1.1%) in the chemotherapy arm. A planned interim analysis using the Lan & DeMets stopping rule at 3.8-year of a median follow up showed significant difference in overall and relapse-free survival between the arms (4-year survival 86.3% chemotherapy vs. 73.6% surgery alone; P=.0176 and 4-year relapse-free survival 84.5% chemotherapy vs. 68.1% surgery alone; P=.0040 respectively). Fourteen pts in chemotherapy arm and 31 pts in surgery alone arm were confirmed to have cancer recurrence. Conclusions: There was definitive benefit in overall and relapse-free survival with this adjuvant chemotherapy. We recommend adjuvant chemotherapy with this regimen for this population in clinical practice, although the planned sample size was not attained. No significant financial relationships to disclose.