| الوصف: |
P Maroto,1 E Esteban,2 E Fernández Parra,3 MJ Mendez-Vidal,4 M Domenech,5 B Pérez-Valderrama,6 V Calderero,7 JL Pérez-Gracia,8 E Grande,9 F Algaba10 1Department of Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, 2Department of Oncology, Nuevo HUCA, Oviedo, 3Department of Oncology, H. U. Nuestra Señora de Valme, Sevilla, 4Department of Oncology, H. U. Reina Sofía, Córdoba, 5Department of Oncology, Hospital de Althaia Xarxa Asistencial Manresa, Barcelona, 6Department of Oncology, H. U. Virgen del Rocio, Sevilla, 7Department of Oncology, H. Fundación Miguel Servet, Zaragoza, 8Department of Oncology, Clinica Universitaria de Pamplona, Pamplona, 9Department of Oncology, H. Ramón y Cajal, Madrid, 10Pathology Unit, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain Background: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel–Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. Objective: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. Methods: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan–Meier method was applied to measure progression-free survival (PFS) and overall survival. Results: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4–13.5 months), median overall survival was 21.8 months (95% CI: 14.7–29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03–6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome.Conclusion: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials. Keywords: c-Myc, clear-cell renal cell carcinoma, HIF, sunitinib |
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