Phase II study of Ccr-based dose-control of S-1 in the first-line chemotherapy of S-1/oxaliplatin (SOX) + bevacizumab regimen for advanced colorectal cancer

Background: In the 1st line therapy of metastatic colorectal cancer(mCRC), SOX+Bevacizumb(Bev) regimen (L-OHP: 130 mg/m2 day 1, Bev: 7.5 mg/kg day 1, S-1: 80, 100, 120 mg*/body days 1–14 repeated every 3 weeks, *According to body surface area, BSA < 1.25 m2, BSA ≥ 1.25 to < 1.5, BSA ≥ 1.5) has been prooved to be non-inferior to mFOLFOX6+Bev with respcet to PFS by the Japanese phase III study, SOFT trial (JapicCTI-090699). In the east-Asian countries, SOX regimen is now widely used in the 1st line treatment of mCRC because of the advantages of the port-free administration in the out-patient clinic. However, in SOFT trial, incidences of grade 3 or higher diarrhea was statistically higher in SOX group than in mFOLFOX6 group (9% vs 3%; p = 0·0040), which was thought to be responsible of S-1. Especially in SOX group, the patients whose creatinine-clearence(Ccr) below 70ml/min, grade 3 or higher diarrhea was significantly by far common than in patients with Ccr above 70ml/min (21.1% vs 5.7%; p = 0.0012). Therefore, it will be suggested that Ccr-based dose-control of S-1 will be effective to decrease severe diarrhea that will lead to the impairment of the compliance of SOX regimen. Trial design: This trial is an open-label, multi-center, phase 2 study. Before administration of SOX regimen, Ccr is measured. The patients with Ccr >_70, the standard dose will be administered, and in the patients with Ccr 70>_60, the level 1 dose control (decrease) will be performed, and in the patients with Ccr 60>_50, the level 2 dose control will be performed (in the patients <50, no administration will be permitted). The primary endpoint is the incidence of grade 3 or higher diarrhea, and the secondary endpoints are SO, PFS, RR, TTF, R0 resectability, ETS. Thirty-five patients are going to be enrolled, and 21 patients have undergone enrollment at the time of submission of the present abstract. Clinical trial identification: UMIN000015446 Legal entity responsible for the study: Kyoto Katsura Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.