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. (25th August 2015)

• Record Type: Journal Article
• Authors: Bilen, Mehmet Asim; Zurita, Amado J.; Ilias-Khan, Nasreen A.; Chen, Hsiang-Chun; Wang, Xuemei; Kearney, Alper Y.; Hodges, Sherie; Jonasch, Eric; Huang, Shixia; Khakoo, Aarif Yusuf; Tannir, Nizar M.
• Is Part Of: Oncologist. Volume 20:Number 10(2015)
• Page Start: 1140
• Page End: 1148
• Publication Date: 2015-08-25
• Subjects: Cytokines and angiogenic factors -- Biomarkers -- Hypertension -- Non-clear cell renal cell carcinoma -- Nitric oxide -- Sunitinib; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2015-0143
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: 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. Implications for Practice: The present study describes the first analysis of hypertension and a relatively large set of circulating cytokines and angiogenic factors in patients with advanced non-clear cell renal cell carcinoma (nccRCC) treated with sunitinib. No association was found between hypertension and patient outcomes. However, a group of candidate circulating biomarkers was identified, in particular, those associated with tumor necrosis factor and CXCR1/2 signaling, with probable biological and clinical significance in nccRCC, warranting confirmation in future studies. Abstract : The significance of hypertension developing during vascular endothelial growth factor receptor tyrosine kinase inhibitor treatment and a group of cytokines and angiogenic factors in advanced non-clear cell renal cell carcinoma patients treated with sunitinib in a phase II study were evaluated. No association between hypertension and survival or response was found. Elevated baseline soluble tumor necrosis factor receptor I, interleukin-8, growth-regulated oncogene, transforming growth factor-a, and VEGFR-2 levels were associated with an increased risk of death.