Identification of predictive circulating biomarkers of bevacizumab-containing regimen efficacy in pre-treated metastatic colorectal cancer patients

Br J Cancer. 2012 Jul 10;107(2):287-90. doi: 10.1038/bjc.2012.242. Epub 2012 Jun 14.

Abstract

Background: To identify whether circulating levels of angiogenesis-related factors may be predictive of bevacizumab efficacy in pre-treated metastatic colorectal cancer (mCRC) patients.

Methods: Pre-treatment serum levels of 24 cytokines were measured using a multiplex bead assay (MBA) in 32 pre-treated mCRC patients treated with irinotecan plus bevacizumab-based salvage therapy. Macrophage-derived chemokine (MDC), interleukins (ILs) 8 and 6 levels were also validated by enzyme-linked immunosorbent assay (ELISA) at different time points during therapy.

Results: Higher epidermal growth factor (EGF) and MDC baseline levels (2.2- and 1.4-fold, respectively) and lower IL-10, IL-6 and IL-8 levels (0.2-, 0.6-, and 0.6-fold, respectively, P<0.05) were observed in patients responding to therapy. Baseline levels of these five serum factors compose a risk signature that may define the subset of patients most likely to benefit from bevacizumab-based therapy in terms of response rate and survival times. A positive correlation was found between MBA and ELISA results (P<0.01). Treatment exposure increased MDC and had opposite effects on IL-8 levels, which were decreased (P<0.05).

Conclusion: This study suggests that a set of inflammatory and angiogenesis-related serum markers may be associated with the efficacy of bevacizumab-containing regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Biomarkers, Tumor / blood*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Chemokine CCL22 / metabolism
  • Cohort Studies
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy*
  • Epidermal Growth Factor / metabolism
  • Female
  • Humans
  • Interleukins / metabolism
  • Irinotecan
  • Male
  • Middle Aged

Substances

  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • Chemokine CCL22
  • Interleukins
  • Bevacizumab
  • Epidermal Growth Factor
  • Irinotecan
  • Camptothecin