TY - JOUR
T1 - Brain metastases from renal cell carcinoma in the era of tyrosine kinase inhibitors
AU - Dudek, Arkadiusz Z.
AU - Raza, Ahmad
AU - Chi, Ming
AU - Singhal, Meghali
AU - Oberoi, Rajneet
AU - Mittapalli, Rajendar K.
AU - Agarwal, Sagar
AU - Elmquist, William F.
PY - 2013/6
Y1 - 2013/6
N2 - Background: The effectiveness of tyrosine kinase inhibitors (TKI) in preventing brain metastases in patients with renal cell carcinoma is unclear. Methods: Preclinical studies were conducted to determine the steady-state brain and plasma concentrations of sorafenib and sunitinib in mice deficient in the drug efflux transporters; p-glycoprotein, and breast cancer resistance protein. A single-institution retrospective analysis of patients treated from 2008 to 2010 was conducted to assess the incidence of brain metastases before and during TKI treatment. Results: Transport of sorafenib and sunitinib across the blood-brain barrier was restricted. Retrospective analysis revealed that the median time to develop metastatic brain disease was 28 months (range, 1-108 months) while on TKI therapy and 11.5 months (range, 0-64 months) in patients who did not receive TKI therapy. The incidence of brain metastases per month in patients not treated with TKI therapy was 1.6 higher than the incidence in patients treated with TKI therapy. Conclusions: Penetration of sorafenib or sunitinib through an intact blood-brain barrier to brain tissue is limited; however, the incidence of brain metastases per unit time is decreased in patients on TKI therapy in comparison with the "cytokine" era.
AB - Background: The effectiveness of tyrosine kinase inhibitors (TKI) in preventing brain metastases in patients with renal cell carcinoma is unclear. Methods: Preclinical studies were conducted to determine the steady-state brain and plasma concentrations of sorafenib and sunitinib in mice deficient in the drug efflux transporters; p-glycoprotein, and breast cancer resistance protein. A single-institution retrospective analysis of patients treated from 2008 to 2010 was conducted to assess the incidence of brain metastases before and during TKI treatment. Results: Transport of sorafenib and sunitinib across the blood-brain barrier was restricted. Retrospective analysis revealed that the median time to develop metastatic brain disease was 28 months (range, 1-108 months) while on TKI therapy and 11.5 months (range, 0-64 months) in patients who did not receive TKI therapy. The incidence of brain metastases per month in patients not treated with TKI therapy was 1.6 higher than the incidence in patients treated with TKI therapy. Conclusions: Penetration of sorafenib or sunitinib through an intact blood-brain barrier to brain tissue is limited; however, the incidence of brain metastases per unit time is decreased in patients on TKI therapy in comparison with the "cytokine" era.
KW - Brain metastases
KW - Drug efflux transporters
KW - Renal cell carcinoma
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84876959042&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876959042&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2012.11.001
DO - 10.1016/j.clgc.2012.11.001
M3 - Article
C2 - 23265925
AN - SCOPUS:84876959042
SN - 1558-7673
VL - 11
SP - 155
EP - 160
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 2
ER -