Exploratory Randomized Phase Ii Trial For Optimizing Treatment Dosage And Duration Of Adjuvant S-1 Plus Oxaliplatin In Patients With Stage Iii Colon Cancer (Soap Trial)

Conventionally, the recommended duration of adjuvant chemotherapy had been 6 months. The recent combined analysis by the IDEA Collaboration for stage III colon cancer suggested that shortening the oxaliplatin-based adjuvant chemotherapy may be possible. Especially, in the IDEA low-risk stage III, 3 months of CAPOX was shown to be non-inferior to 6 months. S-1 and oxaliplatin treatment (SOX) + bevacizumab was shown to be non-inferior to FOLFOX + bevacizumab as first-line chemotherapy in metastatic colorectal cancer patients. The aim of this study was to optimize treatment dosage and duration of adjuvant SOX in patients with stage III colon cancer. This trial was an open-label multi-center randomized phase II study (UMIN000013825). Patients who had undergone curative resection for stage III colon cancer were randomly assigned to 3 months or 6 months of adjuvant SOX delivered every 3 weeks in different doses. Treatment in SOX included a 2-hour intravenous infusion of 130mg/m 2 (3 months) or 100mg/m 2 (6 months) of oxaliplatin on day1 and oral S-1 80mg/m 2 according to BSA twice a day from the evening of day1 to the morning of day15 repeated every 3 weeks. 4 cycles or 8 cycles SOX was administered to patients in the 3 months and 6 months treatment groups, respectively. The primary endpoint was 3-year DFS. The null hypothesis for the primary endpoint was that the 3-year DFS was ≤72% in each arm and was tested with a one-sided significance level of 10%. The secondary endpoints were OS, relative dose intensity (RDI), treatment completion rate, and adverse events (AE). From May 2014, to November 2017, 163 eligible patients were enrolled from 9 institutions in Japan. Eight cases were excluded. Of the 155 patients, 76 were assigned to the 6 months and 79 to the 3 months arm. There were no substantial differences in the baseline characteristics between the two arms. The median follow-up for all patients following randomization was 52.1 months. The 3-year DFS was 75.0% (80%CI 0.6795, 0.8072, p=0.282) in the 6 months and 76.9% (80%CI 0.701-0.8238, p=0.171) in the 3 months arm. 3-year OS was 97.3% (95%CI 0.8962-0.9932) in the 6 months and 97.4% (95%CI 0.9013-0.9935) in the 3 months arm. Treatment completion rate was 73.7% in the 6 months and 86.1% in the 3 months arm (p=0.070). The mean relative dose intensity (RDI) of Oxaliplatin and S-1 were 77.4% and 76.9% in the 6 months and 85.0% and 82.6 in the 3 months arm, relatively (p=0.002, p=0.030). The rate of grade 3 and more AE was 42.1% in the 6 months and 34.2% in the 3 months arm (p=0.326). The 3-year DFS was not significantly superior to 72% in both the 3 months and 6 months arms for the patients of stage III colon cancer. RDI was significantly greater in the 3 months than 6 months arm and the rate of grade 3 or more AE was not significantly different between the two arms. SOX adjuvant chemotherapy for 3 months with 130mg/m2 dose of oxaliplatin was feasible and safe compared to 6 months with 100mg/m2 dose.