Sunitinib malate provides activity against murine bladder tumor growth and invasion in a preclinical orthotopic model.
OBJECTIVE
To evaluate the effects of sunitinib on localized bladder cancer in a mouse orthotopic bladder tumor model.


METHODS
We used an established orthotopic mouse bladder cancer model in syngeneic C3H/He mice. Treatment doses of 40 mg/kg of sunitinib or placebo sterile saline were administrated daily by oral gavage. Tumor volume, intratumoral perfusion, and in vivo vascular endothelial growth factor receptor-2 expression were measured using a targeted contrast-enhanced micro-ultrasound imaging system. The findings were correlated with the total bladder weight, tumor stage, and survival. The effects of sunitinib malate on angiogenesis and cellular proliferation were measured by immunostaining of CD31 and Ki-67.


RESULTS
Significant inhibition of tumor growth was seen after sunitinib treatment compared with the control. The incidence of extravesical extension of the bladder tumor and hydroureter in the sunitinib-treated group (30% and 20%, respectively) was lower than the incidence in the control group (66.7% and 55.6%, respectively). Sunitinib therapy prolonged the survival in mice, with statistical significance (log-rank test, P = .03). On targeted contrast-enhanced micro-ultrasound imaging, in vivo vascular endothelial growth factor receptor-2 expression was reduced in the sunitinib group and correlated with a decrease in microvessel density.


CONCLUSIONS
The results of our study have demonstrated the antitumor effects of sunitinib in the mouse localized bladder cancer model. Sunitinib inhibited the growth of bladder tumors and prolonged survival. Given that almost 30% of cases in our treatment arm developed extravesical disease, sunitinib might be suited as a part of a multimodal treatment regimen for bladder cancer.
Division of Urology, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China.
Eddie Shu-yin
ES
Chan
Amit R
AR
Patel
Donna E
DE
Hansel
William A
WA
Larchian
Warren D
WD
Heston
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib