S-1 Plus Cisplatin-based Chemoradiotherapy After Induction Chemotherapy for Locally Advanced Gastric Adenocarcinoma : Phase II Trial

Though a significant decrease in its incidence over the last 70 years, gastric cancer remains a significant health problem worldwide. Despite the R0 resection and adjuvant chemotherapy, the prognosis for patients with locally advanced GC remains poor, with 5-year survival rate below 60%. Therefore, active strategy to improve survival outcome is ongoing in gastric cancer. Due to the nature of gastric surgery, postsurgical recovery can be avoided by the administration of systemic therapy and/or radiation prior to the surgical procedure. Furthermore, preoperative therapy has the theoretical advantage of treating an untouched tumor (lack of treatment-induced resistance), with intact vascularization and without fibrotic remodeling of the tumor bed due to surgical trauma. These considerations addressed clinical trials incorporating neoadjuvant treatment for gastric cancer.

Preoperative chemotherapy proved superiority to surgery alone in esophagogastric junction cancer Regarding the pattern of failure, locoregional recurrence after surgical resection has been reported 20-50% of cases. To improve local control and survival outcome, chemoradiotherapy in the neoadjuvant or preoperative setting has been widely applied. In recently published meta-analysis, preoperative chemoradiotherapy combined with surgery significantly reduced the 5-year death rate compared to surgery alone (OR 0.57, P=0.001). Ajani et al reported phase II preoperative chemoradiotherapy (5-fluorouracil/cisplatin and 45 Gy radiotherapy) for localized gastric cancer. Among the 34 stage II/III gastric cancer patients, 30% had pathologic complete response and 24% had pathologic partial response (<10% residual carcinoma). Lowy et al also demonstrated 11% and 63% of complete, partial pathologic responses and preoperative chemoradiotherapy was safe and well tolerated. Based on those rationale, 28 clinical trials with neoadjuvant chemotherapy is ongoing for gastric cancer (clinicaltrial.gov) and the investigators' center is also conducting neoadjuvant chemoradiotherapy trial for localized gastric cancer (NCT01269255).Currently, for further improved survival outcome, new cytotoxic compounds such as irinotecan and docetaxel have been combined with 5-FU/cisplatin. However, triplet regimen often burdened with higher toxicity and serious neutropenic infection. Therefore, future trials in neoadjuvant and adjuvant settings need to incorporate new molecular agents which improve efficacy, but less toxicity.