Dual targeting of tumor vasculature: combining Avastin and vascular disrupting agents (CA4P or OXi4503).
BACKGROUND
This study evaluated the therapeutic efficacy of combining vascular disrupting agents with antiangiogenic agents.


METHODS
Human clear cell renal carcinoma (Caki-1) tumors were established in nude mice. Treatments consisted of Avastin (2 mg/kg) administered twice a week; CA4P (100 mg/kg) or OXi4503 (25 mg/kg) administered 3 times a week for a period of 2 weeks; or a combination of Avastin and CA4P or OXi4503. Tumor response was assessed by growth delay.


RESULTS
The tumor growth delays were 8, 6, and 18 days for Avastin, CA4P, and OXi4503, respectively. When the two therapies were combined, there was a significantly greater tumor response than what was achieved with single-agent treatments. For example, Avastin plus CA4P led to a growth delay of 13 days, and 27 days for Avastin plus OXi4503.


CONCLUSIONS
Vascular-directed therapies that include both antiangiogenic and vascular disrupting therapeutics can result in significantly enhanced antitumor effects.
Siemann
Dietmar W
DW
Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL 32610, USA. siemadw@ufl.edu
Shi
Wenyin
W