Changes in circulating pro-angiogenic cytokines, other than VEGF, before progression to sunitinib therapy in advanced renal cell carcinoma patients

Oncology. 2013;84(2):115-22. doi: 10.1159/000342099. Epub 2012 Nov 15.

Abstract

Objectives: This study included a cohort of advanced renal cell carcinoma patients treated with sunitinib. Since resistance to sunitinib may be mediated through angiogenic cytokines other than VEGF, we measured the circulating levels of three pro-angiogenic cytokines: basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and interleukin (IL)-6.

Methods: Cytokines were measured at baseline and on the first day of each treatment cycle until progression in 85 advanced kidney cancer patients treated with sunitinib using a quantitative sandwich enzyme immunoassay (ELISA) technique.

Results: Even though no statistically significant differences in the titers of the three cytokines were observed between baseline and the time of progression in the whole patient cohort, in 45.3, 46.6, and 37.3% of the patients a more than 50% increase between baseline and the time of progression was shown in circulating IL-6, bFGF, and HGF, respectively. Furthermore, this increase was more than 100% in 37.3, 44, and 30.6% of the patients, respectively. We also demonstrated that, in these patients, cytokines tended to increase and to remain high immediately before progression.

Conclusions: In a large percentage of kidney cancer patients, progression is preceded by a significant increase in pro-angiogenic cytokines other than VEGF.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Biomarkers, Tumor / blood*
  • Carcinoma, Renal Cell / blood*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factor 2 / blood*
  • Follow-Up Studies
  • Hepatocyte Growth Factor / blood*
  • Humans
  • Indoles / therapeutic use*
  • Interleukin-6 / blood*
  • Kidney Neoplasms / blood*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neovascularization, Pathologic
  • Prognosis
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inhibitors
  • Biomarkers, Tumor
  • Indoles
  • Interleukin-6
  • Pyrroles
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Hepatocyte Growth Factor
  • Sunitinib