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The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer Results from the Nordic ACT trial

Hansen, Torben Frostrup; Christensen, Rene dePont; Andersen, Rikke Fredslund; Spindler, Karen-Lise Garm; Johnsson, Anders LU and Jakobsen, Anders (2012) In International Journal of Colorectal Disease 27(6). p.715-720
Abstract
Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting. Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the... (More)
Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting. Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher's exact test. The VEGFR-1 319 C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p = 0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs. The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bevacizumab, Biomarkers, Colorectal neoplasms, Haplotypes, Single, nucleotide polymorphisms, Vascular endothelial growth factor, Vascular, endothelial growth factor receptors
in
International Journal of Colorectal Disease
volume
27
issue
6
pages
715 - 720
publisher
Springer
external identifiers
  • wos:000304461400004
  • scopus:84864444473
ISSN
1432-1262
DOI
10.1007/s00384-011-1382-6
language
English
LU publication?
yes
id
a3ad1bd2-88af-4cce-970b-3070572211a1 (old id 2906533)
date added to LUP
2012-08-01 09:46:48
date last changed
2017-06-18 03:23:19
@article{a3ad1bd2-88af-4cce-970b-3070572211a1,
  abstract     = {Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting. Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n = 183) or irinotecan (FOLFIRI or XELIRI, n = 66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher's exact test. The VEGFR-1 319 C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p = 0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC + CA) (39%) and patients homozygous for the A-allele (AA) (56%), p = 0.015. There was no correlation between response rates and the remaining SNPs. The VEGFR-1 319 C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation.},
  author       = {Hansen, Torben Frostrup and Christensen, Rene dePont and Andersen, Rikke Fredslund and Spindler, Karen-Lise Garm and Johnsson, Anders and Jakobsen, Anders},
  issn         = {1432-1262},
  keyword      = {Bevacizumab,Biomarkers,Colorectal neoplasms,Haplotypes,Single,nucleotide polymorphisms,Vascular endothelial growth factor,Vascular,endothelial growth factor receptors},
  language     = {eng},
  number       = {6},
  pages        = {715--720},
  publisher    = {Springer},
  series       = {International Journal of Colorectal Disease},
  title        = {The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer Results from the Nordic ACT trial},
  url          = {http://dx.doi.org/10.1007/s00384-011-1382-6},
  volume       = {27},
  year         = {2012},
}