Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma

Cancer Biol Ther. 2008 Apr;7(4):496-501. doi: 10.4161/cbt.7.4.5624. Epub 2008 Jan 22.


Background: The investigation of angiogenesis inhibitors is of particular interest in renal cell carcinoma (RCC), in which dysregulated blood vessel formation has been correlated with shortened survival. Sorafenib is a novel RAF and VEGF receptor tyrosine kinase inhibitor. We conducted this study to (a) determine if sorafenib is anti-angiogenic, and (b) to relate anti-angiogenic effect to outcome.

Results: Four patients achieved partial response by WHO criteria (ORR 24%). Median time to progression (TTP) was 12.9 months. K(trans) decreased significantly during treatment with sorafenib (60.3% decline, 95% CI 46.1-74.6%). The percent decline in K(trans) and change in tumor size by CT scan were significantly associated with progression-free survival (p = 0.01 and 0.05, respectively). In addition, K(trans) at baseline was also significantly associated with progress-free survival (p = 0.02).

Patients and methods: Seventeen patients with metastatic RCC underwent dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI was used to calculate the gadolinium exchange constant between blood and tumor interstitial tissue, K(trans).

Conclusions: In patients with RCC, inhibition of tumor vascular permeability by sorafenib was associated with improved outcome. Moreover, baseline tumor vascular permeability, expected to be a poor prognosis factor, was a predictive marker of favorable response to therapy.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use*
  • Benzenesulfonates / therapeutic use*
  • Carcinoma, Renal Cell / blood supply
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Kidney Neoplasms / blood supply
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy*
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pilot Projects
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors
  • Pyridines / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Sorafenib
  • Survival Analysis


  • Angiogenesis Inhibitors
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Sorafenib
  • Receptors, Vascular Endothelial Growth Factor
  • Proto-Oncogene Proteins c-raf