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

Keith T. Flaherty, Mark A. Rosen, Daniel F. Heitjan, Maryann L. Gallagher, Brian Schwartz, Mitchell D. Schnall and Peter J. O-wyer

volume 7 | issue 4

April 2008
Pages: 496 - 501

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