Abstract
BackgroundColorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. Some studies have previously shown that IL-17A and IL-17F polymorphisms, respectively rs2275913 and rs763780, are associated with gastric or colorectal cancer risk. Here we aimed at studying the influence of IL-17A-related individual factors on overall survival and progression-free survival in patients with metastatic colorectal cancer treated with a bevacizumab-based chemotherapy.MethodsPre-treatment serum biomarkers were retrospectively evaluated in 122 metastatic colorectal cancer patients treated by bevacizumab in combination with chemotherapy at 2-weeks intervals in a prospective cohort study (NCT00489697). The polymorphisms of IL-17A and IL-17F were analyzed by polymerase chain reaction - restriction fragment length polymorphism. Serum concentrations of Th17-related cytokines were measured by MultiPlex. The impact of individual parameters on overall survival and progression-free survival was assessed using multivariate Cox models.ResultsHigh baseline IL-17A serum concentrations were significantly associated with shorter progression-free survival [p = 0.043]. Other baseline serum Th17-related cytokines and polymorphisms of IL-17 were not associated with overall survival or progression-free survival.ConclusionsIn this ancillary study, baseline serum IL-17A concentration is the only Th17/IL-17 related factor that was significantly associated with the response of patients with metastatic colorectal cancer to bevacizumab. But this main significant result is highly dependent on one case which, if left out, weakens the data. Other clinical studies are required to confirm this association.Trial registrationNCT00489697. June 20, 2007.
Highlights
Colorectal cancer is a major public health issue worldwide
In addition to biomarkers previously assessed, i.e. CarcinoEmbryonic Antigen (CEA), vascular endothelial growth factor (VEGF) and bevacizumab concentrations [7], we studied the influence of baseline serum Th17-related cytokines concentrations and of selected Interleukin-17 A (IL-17A) (G197A, rs2275913) and Interleukin-17 F (IL-17F) (T7488C, rs763780) polymorphisms on clinical outcomes
In addition to the risk factors of progression reported by Caulet et al [7] and regarding this cohort of patients with advanced colorectal cancer treated with a bevacizumabbased regimen, serum IL-17A baseline concentrations were identified as an independent factor and no influence of other Th17/Il-17A-related markers was observed
Summary
Colorectal cancer is a major public health issue worldwide. Interleukin-17 (IL-17) and Th17 (T-helper cell type 17)-related molecules are involved in tumor development and in resistance to bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody used in association with chemotherapy in metastatic colorectal cancer. We aimed at studying the influence of IL-17A-related individual factors on overall survival and progression-free survival in patients with metastatic colorectal cancer treated with a bevacizumab-based chemotherapy. Colorectal cancer is a major public health issue due to its frequency and its severity [1]. Though bevacizumab prolongs survival of patients with metastatic colorectal cancer, some individuals do not respond to treatment [6] and it is difficult to identify at an early stage who will benefit or not from this biopharmaceutical. Bevacizumab pharmacokinetics was influenced by baseline VEGF and CarcinoEmbryonic Antigen (CEA) concentrations and by the number of extra-hepatic metastases These differences in bevacizumab pharmacokinetics between patients are relevant since bevacizumab concentrations are associated with progression-free (PFS) and overall survival (OS) of patients [7]. There is a need to identify other early biomarkers that could be predictive of response to anti-VEGF biopharmaceuticals
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