Pharmacodynamic and pharmacogenetic angiogenesis-related markers of first-line FOLFOXIRI plus bevacizumab schedule in metastatic colorectal cancer.
Br J Cancer
; 104(8): 1262-9, 2011 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-21407216
ABSTRACT
BACKGROUND:
The identification of molecular and genetic markers to predict or monitor the efficacy of bevacizumab (BV) represents a key issue in the treatment of metastatic colorectal cancer (mCRC).METHODS:
Plasma levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble VEGF receptor 2 (sVEGFR-2) and thrombospondin-1 (TSP-1) were assessed by ELISA assay at different time points in a cohort of 25 patients enroled in a phase II trial of GONO-FOLFOXIRI plus BV as first-line treatment of mCRC. VEGF -2578A/C, -1498C/T, -1154A/G, -634C/G and 936C/T; and VEGFR-2 -604A/G, +1192C/T and +1719A/T, polymorphisms were assessed in a total of 54 patients.RESULTS:
Treatment with GONO-FOLFOXIRI plus BV determined a prolonged and significant reduction in plasma free, biologically active VEGF concentration. Interestingly, VEGF concentrations remained lower than at baseline also at the time of PD. Conversely, PlGF levels increased during the treatment if compared with baseline, suggesting a possible role in tumour resistance; moreover, sVEGFR-2 increased at the time of PD, as well as TSP-1. No association of assessed polymorphisms with outcome was found.CONCLUSION:
Our study suggested the possible mechanisms of resistance to combined therapy in those patients with a progressive disease to be tested in ongoing phase III randomised studies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Biomarcadores Tumorais
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Anticorpos Monoclonais
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália