Journal Article

Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer

Kim, M A, Bang, Y-J, Park, S R, Song, H S, Im, S-A, Lee, K H, Han, S-W, Lee, K-W, Choi, I S, Lee, M H, Lee, N-S, Oh, D-Y, Kim, W H, Kim, T-Y

2009

Overview

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- α 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adult / Aged / Antibodies, Monoclonal - administration & dosage / Antibodies, Monoclonal, Humanized / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biological and medical sciences / Biomarkers, Tumor - analysis / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cetuximab / Clinical Study / Drug Resistance / Epidemiology / Female / Fluorouracil - administration & dosage / Gastroenterology. Liver. Pancreas. Abdomen / Humans / Leucovorin - administration & dosage / Liver Neoplasms - chemistry / Liver Neoplasms - drug therapy / Liver Neoplasms - secondary / Male / Medical sciences / Middle Aged / Molecular Medicine / Neoplasm Recurrence, Local - diagnosis / Neoplasm Recurrence, Local - drug therapy / Neoplasm Staging / Oncology / Organoplatinum Compounds - administration & dosage / Peritoneal Neoplasms - chemistry / Peritoneal Neoplasms - drug therapy / Peritoneal Neoplasms - secondary / Prognosis / Prospective Studies / Stomach Neoplasms - chemistry / Stomach Neoplasms - drug therapy / Stomach Neoplasms - pathology / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Survival Rate / Treatment Outcome / Tumors