title: 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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Mehmet Asim
authors: MA
authors: Bilen
authors: 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.
authors: Amado J
authors: AJ
authors: Zurita
authors: 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.
authors: Nasreen A
authors: NA
authors: Ilias-Khan
authors: 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.
authors: Hsiang-Chun
authors: HC
authors: Chen
authors: 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.
authors: Xuemei
authors: X
authors: Wang
authors: 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.
authors: Alper Y
authors: AY
authors: Kearney
authors: 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.
authors: Sherie
authors: S
authors: Hodges
authors: 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.
authors: Eric
authors: E
authors: Jonasch
authors: 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.
authors: Shixia
authors: S
authors: Huang
authors: 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.
authors: Aarif Yusuf
authors: AY
authors: Khakoo
authors: 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.
authors: Nizar M
authors: NM
authors: Tannir
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007211:Indoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects*; D000077210:Sunitinib; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
chemical_list: D020533:Angiogenesis Inhibitors; D016207:Cytokines; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Biomarkers; Cytokines and angiogenic factors; Hypertension; Nitric oxide; Non-clear cell renal cell carcinoma; Sunitinib