1Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo2Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki3Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, Matsuyama4Department of Gastroenterology, Saitama Cancer Center, Kita-adachi5Department of Gastroenterology, Chiba Cancer Center, Chiba6Department of Clinical Oncology, Kobe City Medical Center General Hospital, Kobe7Department of Gastroenterology, Keio University, School of Medicine, Tokyo8Department of Gastroenterology, Showa University, School of Medicine, Tokyo9Department of Clinical Oncology, Tonan Hospital, Sapporo10Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama11Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama12Department of Gastroenterology, Yokohama Municipal Citizen's Hospital, Yokohama13Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi14Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya15JCOG Data Center/Operations Office, National Cancer Center, Tokyo16National Cancer Center, Exploratory Oncology Research and Clinical Trial Center, Kashiwa, Japan
Checking for direct PDF access through Ovid
BackgroundSince the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer.Patients and methodsEndoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point.ResultsMultivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08–1.75; P = 0.010], performance status ≥1 (HR 1.45; 95% CI 1.13–1.86; P = 0.004), and number of metastatic sites ≥2 (HR 1.66; 95% CI 1.28–1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56–1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1.ConclusionThese correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.Clinical Trial NumberC000000062, www.umin.ac.jp.