title: Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.
abstract: This prospective study was conducted with the Korean Cancer Study Group to evaluate the efficacy and safety of cetuximab combined with modified FOLFOX6 (mFOLFOX6) as first-line treatment in recurrent or metastatic gastric cancer and to identify potential predictive biomarkers. Patients received cetuximab 400 mg m(-2) at week 1 and 250 mg m(-2) weekly thereafter until disease progression. Oxaliplatin (100 mg m(-2)) and leucovorin (100 mg m(-2)) were administered as a 2-h infusion followed by a 46-h continuous infusion of 5-fluorouracil (2400 mg m(-2)) every 2 weeks for a maximum of 12 cycles. Biomarkers potentially associated with efficacy were analysed. Among 38 evaluable patients, confirmed response rate (RR) was 50.0% (95% CI 34.1-65.9). Median time-to-progression (TTP) was 5.5 months (95% CI 4.5-6.5) and overall survival (OS) 9.9 months. Eleven patients having tumour EGFR expression by immunohistochemistry with low serum EGF and TGF-alpha levels showed a 100% RR compared to 37.0% in the remaining 27 patients (P<0.001). Moreover, ligand level increased when disease progressed in seven out of eight patients with EGFR expression and low baseline ligand level. No patient exhibited EGFR amplification or K-ras mutations. Gastric cancer patients with EGFR expression and low ligand levels had better outcomes with cetuximab/mFOLFOX6 treatment.
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Chongno-Gu, Seoul, Korea.
authors.forename: S-W
authors.initials: SW
authors.lastname: Han
authors.forename: D-Y
authors.initials: DY
authors.lastname: Oh
authors.forename: S-A
authors.initials: SA
authors.lastname: Im
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.forename: K-W
authors.initials: KW
authors.lastname: Lee
authors.forename: H S
authors.initials: HS
authors.lastname: Song
authors.forename: N-S
authors.initials: NS
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
authors.forename: I S
authors.initials: IS
authors.lastname: Choi
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.forename: M A
authors.initials: MA
authors.lastname: Kim
authors.forename: W H
authors.initials: WH
authors.lastname: Kim
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Bang
authors.forename: T-Y
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D000068818:Cetuximab; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000556:secondary; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil