title: A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer.
abstract: To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes.
  
  
  
  All 61 patients received an initial intravenous (IV) dose of cetuximab (400 mg/m2) and weekly doses (250 mg/m2) thereafter, starting on day 1. On day 2 of each 14-day period, patients received IV irinotecan (180 mg/m2), leucovorin (200 mg/m2), and an IV bolus dose of 5-FU (400 mg/m2) followed by a continuous infusion of 5-FU (2400 mg/m2) for 46 h. The primary endpoint was time-to-progression (TTP).
  
  
  
  The response rate (RR) was 33.3% among 54 evaluable patients. In the intention-to-treat analysis, median TTP was 4.6 months (95% confidential interval [CI]: 3.6-5.6 months) and median overall survival (OS) was 8.6 months (95% CI: 7.3-9.9 months). In univariate analyses, plasma vascular endothelial growth factor (VEGF) levels were correlated with clinical outcome. In patients with low (≤12.6 pg/ml) and high (>12.6 pg/ml) baseline plasma VEGF levels, RR values were 55.0% and 5.3%, respectively (P = 0.001); median TTP values were 6.9 months and 2.8 months, respectively (P = 0.0005); and median OS values were 12 months and 5 months, respectively (P <0.0001). None of these patients exhibited KRAS, BRAF, or PIK3CA mutations.
  
  
  
  Combination therapy comprising cetuximab and mFOLFIRI was well tolerated and active as a second-line treatment for patients with metastatic gastric cancer. Patients with low baseline plasma VEGF levels were associated with better clinical outcomes.
  
  
  
  ClinicalTrials.gov. NCT00699881 . Registered 17 June 2008 (retrospectively registered).
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Oncology, Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China. fudanlijin@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Biomarker; Cetuximab; FOLFIRI; Gastric cancer