Neoadjuvant chemotherapy is an accepted treatment method to improve the survival for advanced gastric cancer in worldwide. This phase II study, KSCC1601, aimed to investigate efficacy and safety of S-1 and Oxaliplatin for locally advanced gastric (LAGC) and esophago-gastric cancer (EGC).
Patients received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 every 3 weeks for 3 courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR) according to the proportion of necrosis in the tumor: grade 0, no necrosis; grade 1a, < 1/3 necrosis; grade 1b, > 1/3 or < 2/3 necrosis; grade 2, > 2/3 or < all necrosis; and grade 3, all parts of the tumors affected by necrosis. A sample size of 46 was set according to one-sided significance level of 0.05 and power of 80% based on an exact binomial distribution, and assuming the null hypothesis of a 30% pRR and an alternative hypothesis of a 50% pRR. The incidence of anastomosis leakage in EGC was the main secondary endpoint. Other secondary endpoints were R0 resection rate, overall survival, relapse free survival and safety.
Between 2016 April and 2017 July, 47 patients (24 EGC, 23 LAGC) were enrolled in this study. All patients were eligible for analysis. 42 patients (89.4%:95%CI 76.9-96.5) underwent surgery, and curative resection was performed in 41 patients. The rate of protocol treatment completeness was 42 patients (89.4%:95%CI 76.9-96.5%). pRR, the primary endpoint (grade 1b to 3), was 25 cases (59.5%:90%CI 45.7-72.3%) of primary lesions. The main toxicities of neoadjuvant chemotherapy were grade 3/4 thrombocytopenia (10.6%), neutropenia (6.4%), anemia (4.3%), grade 3/4 anorexia (12.8%). The number of anastomosis leakage so as to 20 EGC according to the Clavien–Dindo classification was 2 for grade IIIa, 2 for grade IIIb, and 1 for grade IV (25.0%:90%CI 10.4-45.6%). Survival data will be updated in further investigation.
The S-1 and oxaliplatin was well tolerated and is promising as a preoperative chemotherapy regimen for patients with LAGC and EGC.
Clinical trial identification
Legal entity responsible for the study
Yakult Honsha Co., Ltd., Cres Kyushu.
All authors have declared no conflicts of interest.