Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study

PLoS One. 2014 Feb 3;9(2):e87746. doi: 10.1371/journal.pone.0087746. eCollection 2014.

Abstract

Background: We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab.

Patients and methods: A total of 566 patients in the NORDIC VII Study were randomized 1∶1∶1 to arm A (Nordic FLOX), arm B (Nordic FLOX + cetuximab), or arm C (Nordic FLOX + cetuximab for 16 weeks followed by cetuximab alone as maintenance therapy). Pretreatment plasma samples were available from 510 patients. Plasma YKL-40 was determined by ELISA and dichotomized according to the age-corrected 95% YKL-40 level in 3130 healthy subjects.

Results: Pretreatment plasma YKL-40 was elevated in 204 patients (40%), and median YKL-40 was higher in patients with mCRC than in healthy subjects (age adjusted, P<0.001). Patients with elevated YKL-40 had shorter PFS than patients with normal YKL-40 (7.5 vs. 8.2 months; hazard ratio (HR) = 1.27 95% confidence interval (CI) 1.05-1.53 P = 0.013) and shorter OS (16.8 vs. 23.9 months; HR = 1.33, 1.04-1.69, P = 0.024). Multivariate Cox analysis demonstrated that elevated pretreatment YKL-40 was an independent biomarker of short OS (HR = 1.12, 1.01-1.25, P = 0.033). The ratio of the updated plasma YKL-40 (i.e. level after 1, 2, 8 weeks of treatment, and at end of treatment compared to the baseline level) was associated with OS (HR = 1.27, 1.06-1.52, P = 0.011).

Conclusions: Plasma YKL-40 is an independent prognostic biomarker in patients with mCRC treated with first-line oxaliplatin-based therapy alone or combined with cetuximab.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Case-Control Studies
  • Cetuximab
  • Chitinase-3-Like Protein 1
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / secondary
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Lectins / blood*
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prognosis
  • Survival Rate
  • Young Adult

Substances

  • Adipokines
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Lectins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Cetuximab
  • Leucovorin
  • Fluorouracil

Grants and funding

This work was supported by Odense University Hospital and University of Southern Denmark by paid salary to Line Schmidt Tarpgaard. Expenses regarding the YKL-40 analysis were supported from “Joint Proof-of-Concept-Fund, the Ministry of Science, Technology and Innovation, Denmark”. Quidel provided the study with some of the YKL-40 ELISA kits. The NORDIC VII Study received funding by Merck KGaA and Sanofi-Aventis. The study sponsors had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The authors had full access to all the data in the study and had the final responsibility for the decision to submit the manuscript for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.