Dynamics of circulating vascular endothelial growth factor-A predict benefit from antiangiogenic cediranib in metastatic or recurrent cervical cancer patients.
Br J Clin Pharmacol
; 85(8): 1781-1789, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30980733
ABSTRACT
AIMS:
There is a need for predictive and surrogate response biomarkers to support treatment with antiangiogenic vascular endothelial growth factor (VEGF) inhibitors. We aimed to identify a minimally-invasive biomarker predicting benefit from cediranib pretreatment or early during treatment in patients with recurrent or metastatic cervical cancer.METHODS:
Blood samples were collected before treatment, during treatment and upon disease progression where appropriate from patients enrolled in CIRCCa, a randomised phase II trial of carboplatin and paclitaxel with or without cediranib. Plasma concentrations of VEGF-A, VEGF-receptor 2, Ang1 and Tie2 were measured using multiplex enzyme-linked immunosorbent assay. Pretreatment and temporal changes of the biomarkers were investigated using proportional hazard regression and unsupervised clustering analysis.RESULTS:
Samples (n = 556) from 52 patients were analysed. VEGF-receptor 2 (P = .0006) and Tie2 (P = .04) were downregulated following cediranib, while VEGF-A (P = .0025) was upregulated. High Eastern Cooperative Oncology Group performance status (P = .02, hazard ratio [HR] = 2.15, 95% confidence interval [CI] 1.13-4.09) and low pretreatment Tie2 concentrations (P = .003, HR = 0.57, 95%CI 0.39-0.83) were independent prognostic factors associated with reduced progression-free survival. Two patterns of changes in VEGF-A following cediranib were identified. Patients with elevated VEGF-A in the first 3 treatment cycles, regardless of magnitude, had reduced progression-free survival in the placebo arm but improved survival with the addition of cediranib (P = .019, HR = 0.13, 95% CI 0.02-0.71).CONCLUSION:
Patterns of early elevation in plasma VEGF-A should be studied further as a potential biomarker to predict treatment benefit from cediranib.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Saude_da_mulher
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Colo_do_utero
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Tipos_de_cancer
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Colo_do_utero
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Biomarcadores Tumorais
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Neoplasias do Colo do Útero
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Fator A de Crescimento do Endotélio Vascular
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Recidiva Local de Neoplasia
Tipo de estudo:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido