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Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab

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Tumor Biology

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.

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Authors and Affiliations

  1. Medical Oncology Department, Institut Clínic Malalties Hemato-Oncológiques (ICMHO), Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, Villarroel 170, 08036, Barcelona, Spain

    Xabier Garcia-Albeniz, Rosa Gallego, Pere Gascón & Joan Maurel

  2. Gastroenterology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERehd, Barcelona, Spain

    Virginia Alonso-Espinaco & Sergi Castellví-Bel

  3. Medical Oncology Department, Hospital Parc Taulí, Sabadell, Spain

    Carles Pericay

  4. Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain

    Vicente Alonso

  5. Medical Oncology Department, Hospital Clínico Zaragoza, Zaragoza, Spain

    Pilar Escudero

  6. Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain

    Carlos Fernández-Martos

Authors
  1. Xabier Garcia-Albeniz
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  2. Carles Pericay
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  3. Virginia Alonso-Espinaco
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  4. Vicente Alonso
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  5. Pilar Escudero
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  6. Carlos Fernández-Martos
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  7. Rosa Gallego
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  8. Pere Gascón
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  9. Sergi Castellví-Bel
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  10. Joan Maurel
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Corresponding author

Correspondence to Joan Maurel.

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CIBERehd is funded by the Instituto de Salud Carlos III.

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Garcia-Albeniz, X., Pericay, C., Alonso-Espinaco, V. et al. Serum matrilysin correlates with poor survival independently of KRAS and BRAF status in refractory advanced colorectal cancer patients treated with irinotecan plus cetuximab. Tumor Biol. 32, 417–424 (2011). https://doi.org/10.1007/s13277-010-0136-3

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  • DOI: https://doi.org/10.1007/s13277-010-0136-3

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