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 underwentdynamic-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.
RCT Entities:
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.
Authors: James P B O'Connor; Alan Jackson; Geoff J M Parker; Caleb Roberts; Gordon C Jayson Journal: Nat Rev Clin Oncol Date: 2012-02-14 Impact factor: 66.675
Authors: Matthias A Karajannis; Geneviève Legault; Michael J Fisher; Sarah S Milla; Kenneth J Cohen; Jeffrey H Wisoff; David H Harter; Judith D Goldberg; Tsivia Hochman; Amanda Merkelson; Michael C Bloom; Angela J Sievert; Adam C Resnick; Girish Dhall; David T W Jones; Andrey Korshunov; Stefan M Pfister; Charles G Eberhart; David Zagzag; Jeffrey C Allen Journal: Neuro Oncol Date: 2014-05-06 Impact factor: 12.300
Authors: Keith T Flaherty; Sandra J Lee; Fengmin Zhao; Lynn M Schuchter; Lawrence Flaherty; Richard Kefford; Michael B Atkins; Philip Leming; John M Kirkwood Journal: J Clin Oncol Date: 2012-12-17 Impact factor: 44.544