Sunitinib malate (SU-11248) alone or in combination with low-dose docetaxel inhibits the growth of DU-145 prostate cancer xenografts

The aim of the study was to evaluate the activity of the antiangiogenic agent SU-11248 (sunitinib malate, Sutent (R)), alone or in combination with docetaxel. To this end, animals bearing DU-145 human hormone-refractory prostate cancer (HRPC) xenografts were treated with sunitinib (40 mg/kg daily, p.o.), docetaxel (10 or 30 mg/kg/week, i.v.), a combination of sunitinib (40 mg/kg daily) and docetaxel (10 mg/kg/week) or vehicle alone. At the end of the 3-week dosing schedule, single-agent treatment induced a tumor regression of 59%, 49% and 75% for sunitinib, docetaxel 10 mg/kg, and docetaxel 30 mg/kg, respectively. The combination of sunitinib with low-dose (10 mg/kg) docetaxel produced a tumor regression comparable to that obtained with high-dose (30 mg/kg) docetaxel, but tolerability was higher as indicated by mice weight. Both sunitinib and docetaxel inhibited tumor regrowth after initial treatment with the alternate drug. These results suggest that sunitinib alone or in combination with low-dose docetaxel may have a role in the treatment of HRPC. (C) 2008 Elsevier Ireland Ltd. All rights reserved.