Oxaliplatin plus S-1 or capecitabine chemotherapy before or after surgery for locally advanced gastric cancer with D2 lymphadenectomy: a phase II-III randomized trial

INTERVENTION: Eligible patients were randomly assigned to one of the four arms: neoadjuvant SOX (peri‐SOX), neoadjuvant CapeOX (peri‐CapeOX), adjuvant SOX (post‐SOX), and adjuvant CapeOX (post‐CapeOX). Patients receiving neoadjuvant chemotherapy started chemotherapy within 3 days after the laparoscopic exploration; and after 2 cycles of chemotherapy, the clinical stage of the tumor was evaluated before the surgery was performed. Radical dissection was aimed in gastrectomy, with standard D2 lymphadenectomy. Patients receiving adjuvant chemotherapy had surgery immediately after the randomization. After the surgery, patients in neoadjuvant chemotherapy arms received 6 cycles of postoperative chemotherapy, whereas 8 cycles were administered to the adjuvant arms. Patients randomized to SOX regimens received oral S‐1 (80 mg/m2 twice daily on day 1‐14) and intravenous oxaliplatin (130 mg/m2 on day 1) for each cycle, whereas the CapeOX patients received oral capecitabine (1000 mg/m2 twice daily on day 1‐14) and intravenous oxaliplatin (130 mg/m2 on day 1). Dose reduction and interruptions were allowed for potentially serious and life‐threatening adverse events that were determined by clinicians. CONDITION: Locally advanced gastric cancer ; Cancer ; Gastric cancer PRIMARY OUTCOME: Overall survival (time interval from the time of randomization to the date of all‐cause death or last follow‐up). Follow‐up was conducted by phone call every 6 months after completion or termination of treatment. SECONDARY OUTCOME: The secondary endpoints included treatment completion rate, surgical complications, chemotherapy adverse events and pathological complete response rate. Treatment completion rate was recorded when the treatment was completed or stopped. Surgical complications were measured during and after surgery. Complete response rate was reported by pathologists after the surgery. Pathological stage was evaluated according to the 7th edition of the American Joint Committee on Cancer TNM Staging Classification for Carcinoma of the Stomach. The clinical response was evaluated by the Response Evaluation Criteria for Solid Tumors (RECIST) in computed tomography and by the downstaging assessed by endoscopic ultrasound using Choi criteria by the end of the second cycle of neoadjuvant chemotherapy (NACT). Pathology response to NACT was evaluated according to the 3rd English edition of the Japanese Classification of Gastric Cancer. INCLUSION CRITERIA: 1. Aged between 18 and 80 years 2. Pathologically confirmed gastric adenocarcinoma 3. Disease at the clinical stage of resectable advanced gastric cancer (T2‐4NanyM0), without peritoneal metastasis as confirmed by laparoscopy and cytological pathology 4. Eastern Cooperative Oncology Group performance status of 0 or 1 5. No previous treatment history 6. Adequate organ function levels (hematological ANC =1.5x10(9)/l, hemoglobin =9 g/dl, platelets = 100x10(9)/l, hepatic albumin =30 g/l, serum bilirubin =1.5x the upper limit of normal [ULN], AST and ALT =2.5×ULN, ALP =2.5×ULN, TBIL =1.5×ULN, renal serum creatinine <1.5xULN) 7. Adequate lung and heart function, without ECG‐confirmed ischemic change or ventricular arrhythmias