부산대학교 도서관

5113 Background: Several drugs are available for treatment of MRCC and predictive markers to select the most appropriate therapy for each patient are needed to improve efficacy and to avoid unnecessary toxicities and costs.Methods: Serum samples were collected prospectively in 31 patients treated with sunitinib at baseline and at the time of response evaluation by RECIST criteria. Serums of 6 patients with extreme phenotypes of marked responses (3) or clear progressions (3) were analyzed with a Human Cytokine Antibody Array (Series 2000, RayBiotech, Norcross, GA. USA) which evaluates 174 cytokines related to angiogenesis and tumor proliferation pathways and has been validated in clinical studies. Cytokine intensity levels were compared between both groups at baseline and after response evaluation and fold-change differences were calculated. Following array data normalization, the most relevant cytokines based on statistical significance and on biological plausibility, were assessed with ELISA in the whole group of patients and the results were correlated with clinical benefit (response or disease stabilization) or progression.Results: 27 of the 174 cytokines varied significantly between patients presenting response or progression. Six of them (TNF-α, MMP-9, ICAM-1, BDNF, SDF-1α and VEGF) were assessed with ELISA in 22 evaluable patients. TNF-α and MMP-9 baseline levels were significantly increased in non-responders and they were significantly associated with progression-free and overall survival respectively. The area under the ROC curves of TNF-α and MMP-9 as predictive factors of sunitinib clinical benefit were respectively 0.8287 and 0.7685, indicating good accuracy.Conclusions: Baseline serum levels of TNF-α and MMP-9 warrant further study as predictive markers of sunitinib activity in patients with MRCC. Selection of patients with extreme phenotypes seems a valid method to identify potential predictive factors of response. [Table: see text] [Table: see text].