The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414).
Conclusion: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).