Published in:
01-04-2011 | Research Article
Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab
Authors:
Xabier Garcia-Albeniz, Carles Pericay, Virginia Alonso-Espinaco, Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Rosa Gallego, Pere Gascón, Sergi Castellví-Bel, Joan Maurel
Published in:
Tumor Biology
|
Issue 2/2011
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Abstract
The purpose of the study was to prospectively explore the role of serum MMP-7 as a predictive and prognostic marker of anti-epidermal growth factor receptor (EGFR) therapy and irinotecan efficacy in third-line advanced colorectal cancer therapy. One hundred patients were recruited prospectively from six Spanish hospitals. Patients were treated with biweekly irinotecan 180 mg/m2 and cetuximab 400 mg/m2 (loading dose) and weekly cetuximab 250 mg/m2 until progressive disease or unacceptable toxicity. Baseline MMP-7 was determined using a quantitative solid-phase sandwich ELISA. KRAS and BRAF mutational status were also assessed. The clinical endpoints examined were overall survival (OS), progression-free survival (PFS), and response rate. No association between serum MMP-7 and neither KRAS nor BRAF mutational status was found. The multivariate analysis revealed that MMP-7 predicts PFS both in wild-type (WT) KRAS patients (HR 1.03, 95% CI 1.00–1.06; p = 0.046) and in mutant KRAS patients (HR 1.18, 95% CI 1.01–1.35; p = 0.036). The presence of mutant BRAF was associated with shorter PFS (HR 8.49, 95% CI 2.88–25.0; p < 0.001) and worse OS (HR 3.55, 95% CI 1.39–9.09; p = 0.008) in the subset of WT KRAS patients. Serum MMP-7 is associated with PFS in colorectal patients treated with anti-EGFR therapy as third-line treatment independently of KRAS status.