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Protracted Inhibition of Vascular Endothelial Growth Factor Signaling Improves Survival in Metastatic Colorectal Cancer: A Systematic Review.

ABSTRACT: Clinical data suggest that beyond-progression, the blockade of angiogenesis is associated with improved survivals in colorectal cancer. We conducted a systematic review to investigate the therapeutic effects of antiangiogenic drugs administered as later lines of treatment in patients already progressed to a previous anti-VEGF based treatment. An extensive literature search was conducted. Hazard ratios (HR) for progression (PFS) and death (OS) were extracted. An inverse-variance meta-analysis model was implemented. 6 randomized controlled trials were retrieved, including 3407 patients, treated with different antiangiogenic drugs. All of them had progressed during or after a previous line of treatment with bevacizumab. Overall, both PFS (HR=0.63, P <0.001) and OS (HR=0.81, P < 0.001) were significantly increased with the use of antiangiogenic drug. No heterogeneity was observed despite different drugs. Protracted inhibition of the VEGF pathway is associated with a significant improvement of both PFS and OS, independently from the antiangiogenic agent used.

SUBMITTER: Montagnani F

PROVIDER: S-EPMC5490958 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Protracted Inhibition of Vascular Endothelial Growth Factor Signaling Improves Survival in Metastatic Colorectal Cancer: A Systematic Review.

Montagnani Francesco F Di Leonardo Greta G Pino Mariasimona M Perboni Simona S Ribecco Angela A Fioretto Luisa L

Journal of translational internal medicine 20170331 1

Clinical data suggest that beyond-progression, the blockade of angiogenesis is associated with improved survivals in colorectal cancer. We conducted a systematic review to investigate the therapeutic effects of antiangiogenic drugs administered as later lines of treatment in patients already progressed to a previous anti-VEGF based treatment. An extensive literature search was conducted. Hazard ratios (HR) for progression (PFS) and death (OS) were extracted. An inverse-variance meta-analysis mod ...[more]

PMID: 28680835

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Project description:AIM:To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC). METHODS:A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS:In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION:The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.

Dataset Information

Protracted Inhibition of Vascular Endothelial Growth Factor Signaling Improves Survival in Metastatic Colorectal Cancer: A Systematic Review.

Publications

Protracted Inhibition of Vascular Endothelial Growth Factor Signaling Improves Survival in Metastatic Colorectal Cancer: A Systematic Review.

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