Significant effect of VEGFA polymorphisms on the clinical outcome of metastatic colorectal cancer patients treated with FOLFIRI-cetuximab

Pharmacogenomics. 2015 Dec;16(18):2035-43. doi: 10.2217/pgs.15.139. Epub 2015 Nov 30.

Abstract

Aim: The efficacy of a cetuximab-based regimen used to treat metastatic colorectal cancer (mCRC) could be influenced by VEGFA polymorphisms.

Materials & methods: We studied the effects of five polymorphisms in the VEGFA gene (-2549D/I, -1154G/A, -460T/C, +405G/C and +936C/T) on the outcome of 98 mCRC patients treated with FOLFIRI plus cetuximab.

Results: Patients homozygous for the -2549D, -1154G and -460T alleles did exhibit higher response rates to treatment and longer progression-free survival compared with others. In addition, the DGTGC and IGCGC haplotypes were significantly associated with a lower risk of disease progression.

Conclusion: These findings suggest that VEGFA genetic variations might influence response/resistance of FOLFIRI plus cetuximab treatment in mCRC patients.

Trial registration: ClinicalTrials.gov NCT00559741.

Keywords: SNPs; VEGFA; biomarkers; cetuximab; colorectal cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Cetuximab / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Leucovorin / therapeutic use
  • Male
  • Neoplasm Metastasis
  • Polymorphism, Genetic
  • Retrospective Studies
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cetuximab
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol

Associated data

  • ClinicalTrials.gov/NCT00559741