Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab
| Autor: | Maria Laura De Marchis, Girolamo Del Monte, Vincenzo Formica, Italia Grenga, Mario Roselli, Fiorella Guadagni, Giorgia Ludovici, Raffaele Palmirotta, Annalisa Savonarola, Michele Schirru |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Male Vascular Endothelial Growth Factor A Colorectal cancer Aged 80 and over Multivariate Analysis Alleles Middle Aged Camptothecin Colorectal Neoplasms Female Polymorphism Single Nucleotide Fluorouracil Predictive Value of Tests Disease-Free Survival Humans Antineoplastic Agents Antineoplastic Combined Chemotherapy Protocols Aged Proportional Hazards Models Adult Antibodies Monoclonal Neoplasm Metastasis Pharmacogenetics chemistry.chemical_compound bevacizumab metastatic colorectal cancer patients predictive markers vegf gene polymorphisms Monoclonal Clinical endpoint 80 and over Hazard ratio Gastroenterology Single Nucleotide Bevacizumab Vascular endothelial growth factor FOLFIRI medicine.drug medicine.medical_specialty Antibodies Monoclonal Humanized Irinotecan Antibodies Settore MED/01 - Statistica Medica Internal medicine medicine Polymorphism business.industry medicine.disease Radiography chemistry business |
| Popis: | The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients. Forty MCRC patients eligible for a first-line therapy were enrolled in this prospective trial and treated with FOLinate/Fluorouracil/Irinotecan (FOLFIRI) + Bev (male/female = 22:18, age (median) = 61 years). Eight VGPs within the promoter/5’UTR region were evaluated in patient blood samples. Primary endpoint was association between VGPs and median progression-free survival (mPFS). Overall radiological response rate (ORR), overall survival (OS), and toxicity were assessed as secondary outcomes. VGPs −2578, −1512, −1451, −1411, and −460 were in complete linkage disequilibrium and therefore analyzed as haplotype (two variants: Haplo1: A-18 bp insertion-T-4G-C and Haplo2: C-18 bp deletion-C-5G-T, respectively). Seventeen patients Haplo2/Haplo2 had significantly shorter mPFS compared to 23 patients Haplo1/Haplo1 or Haplo1/Haplo2 (mPFS, 9 vs. 15.4 months, respectively, p = 0.02; hazard ratio (HR), 2.64). Also, VGPs −152 (G/G vs. G/A + A/A) and −1154 (G/G vs. G/A + A/A) were significantly associated with PFS (mPFS, 8.9 vs. 15.4 months, p = 0.007; HR, 3.53 and 9.8 vs. 16 months, p = 0.03, HR, 2.32, respectively). In the multivariate analysis including also biochemical variables known to influence prognosis, VGP −1154 retained an independent predictive value for mPFS (G/G over G/A + A/A = HR, 4.43; p = 0.02). With regard to ORR, only VGP −634 was significantly associated with response (G/G vs. G/C + C/C = 64% vs. 14%, p = 0.03). No significant influence on OS and toxicity by the investigated VGPs was observed. Although these data need to be confirmed in larger trials, investigation of germline VGPs may help identify patients who are more sensitive to anti-VEGF agents. |
| Databáze: | OpenAIRE |
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