title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  In patients with metastatic CRC, high pretreatment serum IL-6 levels were associated with a poor outcome and bevacizumab resistance.
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. mshara@med.nagoya-cu.ac.jp.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Nagasaki
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shiga
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Gastroenterological Surgery, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takeyama
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Bevacizumab; Chemo-resistance; Colorectal cancer; Interleukin-6 (IL-6)