Current status and future prospect of periopertive chemotherapy- Towards a fusion of Eastern and Western

Abstract

Substantial efforts had been paid for developing perioperative chemotherapy to improve the treatment results of gastric cancer. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy is considered to be the standard. However, these strategies may not be extrapolated to Japan. In Japan, based on the ACTS-GC results, several attempts have been made according to the stage of the patients. In Stage II, effort has been focused on reducing the toxicity of S-1. Japan Clinical Oncology Group (JCOG) conducted randomized controlled trial (RCT) for evaluating the non-inferiority of 4 course S-1 to standard 8 courses S-1 in Stage II gastric cancer (JCOG1104). On the contrary, more aggressive treatment is preferred for Stage III gastric cancer. One candidate is adjuvant chemotherapy with doublet regimen. Based on the CLASIC trial, phase II trials evaluating the feasibility of CapeOX and SOX had been performed in Japan. JCOG is now planning to perform a RCT comparing S-1 alone versus doublet for Stage III gastric cancer. Other promising candidate is the neo-adjuvant chemotherapy (NAC). JCOG had carried out several phase II studies for marginally resectable cancer and demonstrated improvement of survival. However, solid evidence of survival benefit is lacking until the results of phase III trial (JCOG0501) will be disclosed. In addition, to explore the subjects for NAC, accurate preoperative diagnosis is essential. JCOG had performed observational study to confirm the preoperative staging and proceeded to perform RCT with NAC for cT3-4, cN1-3 patients (JCOG1509). Introducing molecular targeting agents in perioperative treatments will also be the promising strategy. JCOG 1301 is a randomized phase II trial evaluating the efficacy of neo-adjuvant trastuzumab for HER2 positive cancer. In this trial, pathological central review and combined analysis with INNOVATION trial is planning in collaboration with EORTC.