IL-8 and eNOS polymorphisms predict bevacizumab-based first line treatment outcomes in RAS mutant metastatic colorectal cancer patients

Concetta Santonocito, Giovanni Schinzari, Mariantonietta Di Salvatore, Armando Orlandi, Ernesto Rossi, Manlio Caporale, Donatella Guarino, Michele Basso, Ettore Domenico Capoluongo, Filippo Pietrantonio, Marzia Del Re, Rosa Berenato, Marta Caporale, Antonia Martinetti, Roberta Mennitto, Alessia Mennitto, Ilaria Bossi, Romano Danesi, Filippo De Braud

Risultato della ricerca: Contributo in rivistaArticolo in rivista

20 Citazioni (Scopus)

Abstract

Background: Predictive biomarkers of efficacy and toxicity of bevacizumab have not yet been validated. This study assessed the influence of IL-8, eNOS and VEGF-A polymorphisms in RAS mutated metastatic colorectal cancer patients receiving bevacizumab-based chemotherapy. Methods: 120 patients treated with first-line combination FOLFOX6 plus bevacizumab were included. A historical cohort of 112 RAS mutated colorectal cancer patients treated with FOLFOX6 alone served as control group. The following SNPs were analyzed: IL-8 c.-251T>A; eNOS c.-786T>C and c.-894G>T; VEGF-A c.936C>T, c.958T>C, c.1154A>G and c.2578C>A. Correlation of SNPs, baseline IL-8 serum levels and bevacizumab-efficacy was done. Results: In the bevacizumab group, carriers of the IL-8 alleles c.-251TA+ AA showed a shorter PFS (P=0.002) and OS (P=0.03) compared to TT alleles. Patients with pre-treatment IL-8 < 18.25 pg/ml showed significantly longer median PFS and OS (PFS: 10.9 vs 7.6 months, P=0.005; OS: 30.7 vs 18.2 months, P<0.001) compared to patients with IL-8 higher levels (>18,25 pg/ml). IL-8 c.-251TA+ AA carriers had significantly higher IL-8 levels (P<0.0001). Multivariate analysis confirmed association of IL-8 polymorphism with PFS, and of IL-8 baseline levels with both PFS and OS. IL-8 SNP did not affect the outcome in the control group. The eNOS polymorphism c.-894G>T was found associated with higher severe toxicity (P=0.0002) in patients carrying the c.-894TT genotype. Conclusions: Although our data need prospective validation, IL-8 and eNOS SNPs may be have a role as predictive biomarkers for bevacizumab efficacy and toxicity.
Lingua originaleEnglish
pagine (da-a)16887-16898
Numero di pagine12
RivistaOncotarget
Volume8
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • bevacizumab
  • single nucleotid polymorphisms

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