History and emerging trends in chemotherapy for gastric cancer

Chemotherapy is indispensable for gastric cancer. For unresectable and/or recurrent gastric cancer, first-line chemotherapy consists of multidrug regimens including oral 5-FU agents such as S1/Xeloda and platinum preparations, as well as Trastuzumab, which is effective in HER2-positive cases. Second- and third-line chemotherapy regimens include taxanes, Ramucirumab (R-mab), and Nivolumab (N-mab), which have different mechanisms of action from first-line chemotherapy. R-mab is molecularly targeted to vascular endothelial growth factor receptor 2 in the host cells, but its indication is not conditional. For resectable gastric cancer, in Eastern countries, postoperative adjuvant chemotherapy has been successful, including S1, Docetaxel/S1 (DS), and Xeloda/Oxaliplatin (Xelox) regimens, whereas, in Western countries, the 5-FU/Leucovorin/Oxaliplatin/Docetaxel (FLOT) regimen was recently shown to be effective in the perioperative chemotherapy setting. Most recently, however, in Eastern countries, perioperative SOX was demonstrated to be effective in specific advanced gastric cancer. For stage IV gastric cancer, new therapeutic strategies have been proposed such as neoadjuvant chemotherapy and conversion surgery, and cures can be conditionally obtained. Recent genomic understanding of gastric cancer proposed a diversity of molecular targets by molecular profiling. Such optimized chemotherapy regimens, according to the specific clinical situations, have been rigorously established for the best survival of advanced gastric cancer.