The ACTS-GC trial suggested that adjuvant chemotherapy with S-1 should be adopted as the standard treatment for stage II/III gastric cancer after curative D2 gastric dissection. In the JCOG9912 trial (5-FU vs CPT-11+CDDP (CP), 5-FU and vs S-1), the MSTs were 9.0, 12.1, and 10.5 months for 5-FU, CP, and S-1, respectively, with S-1 demonstrating significant non-inferiority to 5-FU, while CP did not show statistically significant superiority to 5-FU. In the SPIRITS trial comparing S-1 alone with S-1+CDDP, the MSTs were 11.0 and 12.0 months for S-1 and S-1+CDDP, respectively, and S-1+CDDP showed statistically significant superiority to S-1 monotherapy. The GC0301/TOP-002 trial compared CPT-11+S-1(IRI-S)to S-1 alone in advanced gastric cancer patients. An analysis revealed an ORR of 26.9% for the S-1 monotherapy arm and 41.5% for the IRI-S arm (p=0.035). However, IRI-S did not show statistically significant superiority to S-1 alone in OS. On the basis of these results, S-1+CDDP was adopted as the standard cancer chemotherapy regimen for inoperable and recurrent gastric cancer in Japan. Thus, in the next revision, the contents of the description of the Japanese Guidelines for Treatment of Gastric Cancer (2nd Edition) will be changed. Now, the second-line treatment and the biological molecular targeting agents-based drug medicine treatment development are continued with an eye to the future.