Hypertension and Circulating Cytokines and Angiogenic Factors in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma Treated With Sunitinib: Results From a Phase II Trial.

Autor:	Bilen MA; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Zurita AJ; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Ilias-Khan NA; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Chen HC; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Wang X; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Kearney AY; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Hodges S; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Jonasch E; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Huang S; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Khakoo AY; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA., Tannir NM; Division of Cancer Medicine, Department of Genitourinary Medical Oncology, Department of Cardiology, and Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Amgen, Inc., San Francisco, California, USA ntannir@mdanderson.org.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2015 Oct; Vol. 20 (10), pp. 1140-8. Date of Electronic Publication: 2015 Aug 25.
DOI:	10.1634/theoncologist.2015-0143
Abstrakt:	Background: We evaluated the significance of hypertension developing during vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (VEGFR-TKI) treatment and a group of cytokines and angiogenic factors (CAFs) in advanced non-clear cell renal cell carcinoma (nccRCC) patients treated with sunitinib in a phase II study. Materials and Methods: Using multiplex assays, we analyzed the levels of 38 CAFs in plasma at baseline and after 4 weeks of sunitinib therapy. Sunitinib benefit was defined as a partial response or stable disease using the Response Evaluation Criteria in Solid Tumors lasting ≥4 months. Cox proportional hazards regression models were used to assess the associations among hypertension, CAFs, and progression-free (PFS) and overall survival (OS). Results: Fifty-seven patients were evaluable; 53 had baseline CAF levels available. The median PFS and OS were 2.9 months (95% confidence interval [CI], 1.4-5.5) and 16.8 months (95% CI, 10.7-27.4), respectively. Sunitinib benefit was observed in 21 patients (37%). However, 33 patients (60%) developed hypertension during treatment, although no association was found with survival or response. Elevated baseline soluble tumor necrosis factor (TNF) receptor I, interleukin-8, growth-regulated oncogene, transforming growth factor-α, and VEGFR-2 levels were associated with an increased risk of death on multivariate analysis. Conclusion: We found no association between the development of hypertension and survival or sunitinib benefit in advanced nccRCC. TNF and angiogenic/immunomodulatory mediators were identified for evaluation as markers of prognosis and VEGFR-TKI benefit in future studies. (©AlphaMed Press.)
Databáze:	MEDLINE
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