Format

Send to

Choose Destination
Oncologist. 2015 Oct;20(10):1140-8. doi: 10.1634/theoncologist.2015-0143. Epub 2015 Aug 25.

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.

Author information

1
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.
2
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.

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.

KEYWORDS:

Biomarkers; Cytokines and angiogenic factors; Hypertension; Nitric oxide; Non-clear cell renal cell carcinoma; Sunitinib

PMID:
26306901
PMCID:
PMC4591942
DOI:
10.1634/theoncologist.2015-0143
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center