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), 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 10mg/kg, and docetaxel 30 mg/kg, respectively. The combination of sunitinib with low-dose (10mg/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.
Cumashi
Albana
A
Department of Oncology and Neurosciences, "G. D'Annunzio" University and Foundation Chieti-Pescara, Via dei Vestini 5, Chieti 66013, Italy.
Tinari
Nicola
N
Rossi
Cosmo
C
Lattanzio
Rossano
R
Natoli
Clara
C
Piantelli
Mauro
M
Iacobelli
Stefano
S
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage; D000077210:Sunitinib; D043823:Taxoids / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D000077210:Sunitinib