High serum levels of interleukin-6 in patients with advanced or metastatic colorectal cancer: the effect on the outcome and the response to chemotherapy plus bevacizumab

Surg Today. 2017 Apr;47(4):483-489. doi: 10.1007/s00595-016-1404-7. Epub 2016 Aug 22.

Abstract

Purpose: We evaluated the relationship of the pretreatment serum IL-6 levels with the outcome and treatment response in patients with advanced or metastatic colorectal cancer (CRC) who underwent bevacizumab-containing chemotherapy.

Methods: In this retrospective study, the pretreatment serum IL-6 and plasma vascular endothelial growth factor (VEGF) levels were measured in 113 patients with metastatic CRC. The cut-off values for these measurements, as determined by a receiver operating characteristic curve analysis, were 4.3 and 66 pg/mL, respectively. The median follow-up period was 19 months (range 1-40 months). Sixty-three patients had primary cancer, and 38 had a metachronous recurrence. Thirty patients underwent curative resection, and 71 underwent chemotherapy, 53 of whom received bevacizumab-containing chemotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and multivariate Cox proportional hazards regression analyses.

Results: The plasma VEGF levels and positive KRAS mutation status were not associated with the outcomes. However, high serum IL-6 levels were significantly associated with poorer OS and PFS in comparison to low serum IL-6 levels. A Cox proportional hazards regression analysis showed that high serum IL-6 levels were an independent risk factor for a poor outcome.

Conclusion: In patients with metastatic CRC, high pretreatment serum IL-6 levels were associated with a poor outcome and bevacizumab resistance.

Keywords: Bevacizumab; Chemo-resistance; Colorectal cancer; Interleukin-6 (IL-6).

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage*
  • Biomarkers, Tumor / blood*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • ROC Curve
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Biomarkers, Tumor
  • IL6 protein, human
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • Bevacizumab