Impact of dihydropyrimidine dehydrogenase status of biopsy specimens on efficacy of irinotecan plus cisplatin, S-1, or 5-FU as first-line treatment of advanced gastric cancer patients in JCOG9912

4535 Background: JCOG9912 (randomized phase III trial) showed a significant non-inferiority of S-1 to 5-FU (P<0.001); however, either S-1 or irinotecanplus cisplatin (IP) failed to show superiority to 5-FU (P=0.034 and 0.055, respectively) in overall survival. Excision repair cross-complementinggroup 1 ( ERCC1), thymidylate synthase(TS) and dihydropyrimidine dehydrogenase(DPD) are reportedly related to outcome of advanced gastric cancer (AGC) patients (pts) treated with IP or 5-FU. Efficacy analyses are performed to evaluate the status of ERCC1, TS, DPD and 5 biomarkers related to anticancer drug sensitivity in first-line pts treated with IP, S-1, or 5-FU monotherapy under controlled conditions. Methods: Blocks from endoscopic biopsy specimens of primary lesions before chemotherapy were available from 365 of 704 pts in JCOG9912. Using laser-captured microdissectionand real-time RT-PCR, we analyzed mRNA expression of ERCC1, TS, DPD in paraffin-embedded specimens. Expression levels of each gene were cat...