Preoperative chemotherapy (CTX) versus preoperative chemoradiotherapy (CRTX) in locally advanced esophagogastric adenocarcinomas: First results of a randomized phase III trial

Abstract

4511 Background: Perioperative treatment is common in localized adenocarcinomas of the upper GI-tract. By now, there is no randomized data about the contribution of preoperative radiotherapy additional to chemotherapy. Methods: Based on phase II results of our group we targeted 394 patients to test whether chemoradiation will increase the 3-year survival rate by 10% compared with chemotherapy. Patients with stage T3–4 NX M0 according to EGD, EUS, CT and laparoscopy were included. Patients were randomized to treatment with either (arm A) 2.5 courses of chemotherapy (cisplatin 50mg/m2, d 1,15,29, folinic acid 500 mg/m2 and 5-FU 2g/m2 24h-infusion, weekly times 6, qd 49 or (arm B) 2 courses of the same chemotherapy followed by three weeks of chemoradiotherapy (30 Gy, cisplatin 50 mg/m2 d 2+8 and etoposide 80 mg/m2 d 3–5). Epoetin alpha was recommended to keep the hemoglobin above 12.5 g/dl. Tumor resection was planned 3 to 4 weeks after the end of preoperative therapy for both groups. Results: A total of 126 patients were randomized into the study between 12/00 and 12/05 when the trial was closed due to poor accrual. 120 pts. were eligible (CTX 60, CRTX 60). The toxicitiy of CTX was low. Severe leucocytopenia and thrombocytopenia was 35% and 16%, respectively during CRTX. Until 12/06 ninety pts. underwent surgery and had complete reports. A complete resection was possible in 77% and 85% of operated pts. in arm A and arm B, respectively. The rate of complete histologic response was 2.5% after CTX and it reached 17% after CRTX (p=0.06). Despite increased postoperative mortality after chemoradiotherapy (5 vs. 2 pts.) the median survival time (32.8 mo) and the 3- year survival rate (43%) were improved in this patients group compared with patients of arm A (21.1 mo, 27%)(logrank p=0.14). Conclusions: This randomized study demonstrates that albeit its increased mortality preoperative chemoradiotherapy appears to prolong survival compared with preoperative chemotherapy in locally advanved esophago-gastric adenocarcinomas. Although accrual was below that planned, the observed difference in survival is clinically important and calls for further randomized trials in patients with this disease. No significant financial relationships to disclose.