Molecular Determinants of Cetuximab Efficacy

• DOI: 10.1200/jco.2005.09.100
• Publication Date: 2005-05-20T23:31:45Z
• Authors: Daniel Vallböhmer; Wu Zhang; Michael Gordon; Dong Yun Yang; Jim Yun; Oliver A. Press; Katrin E. Rhodes; Andy E. Sherrod; Syma Iqbal; Kathleen D. Danen...; Susan Groshen; Heinz-Josef Lenz
• Keywords: Log-rank test

Purpose To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial (VEGF), all members the EGFR signaling pathway, are associated with clinical outcome in patients EGFR-expressing metastatic colorectal cancer (CRC) treated cetuximab. Patients Methods Thirty-nine CRC, refractory to both irinotecan oxaliplatin, were enrolled on IMCL-0144 single-agent The intratumoral CCND1, Cox-2, EGFR, IL-8, VEGF assessed from paraffin-embedded tissue samples using laser-capture microdissection quantitative real-time polymerase chain reaction. Results There 21 women 18 men a median age 64 years (range, 35 83 years). Higher gene resistance cetuximab (P = .038; Kruskal-Wallis test). combination low IL-8 was significantly overall survival (13.5 v 2.3 months; P .028; log-rank Both findings independent skin toxicity that itself correlated survival. lower amount had longer compared higher (7.3 2.2 .09; Cox-2 rate grade 3 reactions under treatment. Conclusion This pilot study suggests CRC may be useful markers