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, Peter J. O'Dwyer

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)496-501
Number of pages6
JournalCancer Biology and Therapy
Volume7
Issue number4
DOIs
StatePublished - Jan 1 2008

Fingerprint

Renal Cell Carcinoma
Disease-Free Survival
Magnetic Resonance Imaging
Capillary Permeability
Neoplasms
Vascular Endothelial Growth Factor Receptor
Angiogenesis Inhibitors
Survival
Gadolinium
Therapeutics
Protein-Tyrosine Kinases
Blood Vessels
sorafenib

Keywords

  • DCE-MRI
  • Renal cell carcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Flaherty, K. T., Rosen, M. A., Heitjan, D. F., Gallagher, M. L., Schwartz, B., Schnall, M. D., & O'Dwyer, P. J. (2008). Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma. Cancer Biology and Therapy, 7(4), 496-501. https://doi.org/10.4161/cbt.7.4.5624

Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma. / Flaherty, Keith T.; Rosen, Mark A.; Heitjan, Daniel F.; Gallagher, Maryann L.; Schwartz, Brian; Schnall, Mitchell D.; O'Dwyer, Peter J.

In: Cancer Biology and Therapy, Vol. 7, No. 4, 01.01.2008, p. 496-501.

Research output: Contribution to journalArticle

Flaherty, Keith T. ; Rosen, Mark A. ; Heitjan, Daniel F. ; Gallagher, Maryann L. ; Schwartz, Brian ; Schnall, Mitchell D. ; O'Dwyer, Peter J. / Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma. In: Cancer Biology and Therapy. 2008 ; Vol. 7, No. 4. pp. 496-501.
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