TY - JOUR
T1 - Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma
AU - Flaherty, Keith T.
AU - Rosen, Mark A.
AU - Heitjan, Daniel F.
AU - Gallagher, Maryann L.
AU - Schwartz, Brian
AU - Schnall, Mitchell D.
AU - O'Dwyer, Peter J.
N1 - Funding Information:
This study was supported by Bayer Pharmaceuticals. This work was presented in preliminary form at the ASCO annual meeting in 2005.
PY - 2008/4
Y1 - 2008/4
N2 - 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 Ktrans and change in tumor size by CT scan were significantly associated with progression-free survival (p = 0.01 and 0.05, respectively). In addition, Ktrans 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, Ktrans. 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.
AB - 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 Ktrans and change in tumor size by CT scan were significantly associated with progression-free survival (p = 0.01 and 0.05, respectively). In addition, Ktrans 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, Ktrans. 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.
KW - DCE-MRI
KW - Renal cell carcinoma
KW - Sorafenib
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U2 - 10.4161/cbt.7.4.5624
DO - 10.4161/cbt.7.4.5624
M3 - Article
C2 - 18219225
AN - SCOPUS:45349107777
SN - 1538-4047
VL - 7
SP - 496
EP - 501
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 4
ER -