Final results of a randomized trial comparing preoperative 5-fluorouracil (F)/cisplatin (P) to surgery alone in adenocarcinoma of stomach and lower esophagus (ASLE): FNLCC ACCORD07-FFCD 9703 trial

4510 Background: The combination of 5FU in continuous infusion and cisplatin (FP) is one of the most active regimen in advanced ASLE. The trial was designed to evaluate the impact on survival of 2–3 cycles of preoperative FP in resectable ASLE. Methods: Patients (pts) with resectable adenocarcinoma of the stomach (S) without cardia involvement, cardia (C) or lower esophagus (LE), age ≤ 75 yrs, WHO performance status (PS) < 2 were eligible. Pts were centrally randomized between surgery alone (arm 1) and preoperative FP (arm 2). Chemotherapy (CT) included 2–3 cycles of P (100 mg/m2) and F (800 mg/m2 d1-d5 continuous infusion) every 28 days. Post- operative FP was recommended in arm 2 in case of response to FP preoperative or stable disease with pN+. The main endpoint was overall survival. Comparison of disease-free survival (DFS) used 6-month landmark method and two-sided logrank test. Results: Between 1995 and 2003, 224 pts (arm 1 = 111 pts, arm 2 = 113 pts) were randomized from 28 centers. Initial pts characteristics were equally balanced for age (mean, 61 yrs), gender (83 % male), PS (75 % WHO 0), tumor site (S = 25 %,C = 64 %, LE = 11 %). Median follow-up was 5.7 years. In arm 2, FP was given before surgery in 109 pts (98 pts > 2 cycles) and after surgery in 54 pts. R0 resection rate was 73 % in arm 1 versus 84 % in arm 2 (p=0.04). Preoperative CT improved DFS (p=0.003): hazard ratio (HR) 0.65 (95%CI 0.48–0.89), with 3 and 5-year DFS of 25% (18–34%) and 21% (14–30%) in arm 1 vs. 40% (31–49%) and 34% (26–44%) in arm 2, respectively. HR of death was 0.69 (0.50–0.95, p=0.02) with 3 and 5- year overall survival (OS) of 35% (27–44%) and 24% (17–33%) vs. 48% (39–57%) and 38% (29–47%), respectively. Similar results on OS were observed using Cox model stratified on center and adjusted on gender, age, performance status, and tumor localization. No significant variation of chemotherapy effect with tumor localization was observed. Conclusions: Preoperative chemotherapy using 5- fluorouracil/cisplatin improves disease-free and overall survival in patients with resectable adenocarcinoma of stomach and lower esophagus. No significant financial relationships to disclose.