We reported S-1/LV regimen yielded promising ORR, PFS, TTF, and OS, without combination with platinum, taxane, irinotecan, or trastuzumab as first-line treatment. In previous phase II studies of S-1 monotherapy in AGC and previous S-1 monotherapy arms of phase III JCOG9912 study, SPIRITS study, SC-101 study, GC0301/TOP-002 study, and START study, conventional dose for 4 weeks followed by 2-week rest was usually given [18–22]. The 2-week S-1/LV here was generally more effective, with a less dose intensity than S-1 monotherapy in these studies. LV can enhance the efficacy of 5-FU by maintaining the plasma 5-FU concentration . Similarly with the previous trial of S-1/LV in mCRC , S-1/LV regimen here also demonstrated better efficacy and safety compared with previously reported UFT/LV in AGC [3, 24]. S-1/LV also showed more potential than 5-FU/LV plus oxaliplatin that we reported in terms of efficacy and safety .