The Feasibility of BCG and Sunitinib Combination Therapy for Transitional Cell Carcinoma

Dah-Shyong Yu, Szu-Yuan Ping, Chia-Lun Wu, Hong-I Chen, Sun-Yran Chang, Cheng-Ping Ma
2011 Urological Science  
Objective: Currently, intravesical bacille Calmette-Guérin (BCG) instillation is the standard treatment for patients with an intermediate to high risk of bladder cancer. Nevertheless, BCG-refractory generation is a common process during treatment. We hypothesized that sunitinib, a vascular endothelial growth factor (VEGF) receptor inhibitor, can synergistically enhance the immunotherapeutic effect of BCG on bladder tumor growth. Materials and Methods: The 50% inhibitory concentration (IC 50 )
more » ... BCG and sunitinib in various transitional cell carcinoma (TCC) cell lines was determined by the MTT method. The therapeutic effects of BCG, sunitinib, and their combination on MBT-2 tumors were investigated in both orthotopic bladder cancer and subcutaneously inoculated tumor models in mice. Evaluated parameters included the tumor growth rate and tumor burden in the bladder, tumor volume in the subcutaneous site, survival rate, serum cytokine changes, and mean vascular density in tumor tissues. Results: BCG and sunitinib showed in vitro cytotoxicity to tested TCC cell lines with slight variations in IC 50 . Sunitinib had an in vitro synergistic effect on BCG cytotoxicity in TCC cells. BCG and sunitinib had individual tumor suppression activities in mice MBT-2 tumors in both the orthotopic and subcutaneous models. Surprisingly, synchronous combination treatment using BCG and sunitinib did not demonstrate synergistic suppression efficacy in animal tumor models. Inhibition of tumor growth, increased survival rate, and decreased mean vascular density were observed in mice treated with BCG, sunitinib, and synchronous cotreatment. In contrast, no therapeutic efficacy was seen in mice treated with BCG and sunitinib metachronously. Conclusions: BCG and the VEGF receptor inhibitor sunitinib had significant suppressive effects in mice bladder cancer models when administered individually. The underlying mechanisms by which they counteract cytotoxicity and the interaction of BCG and sunitinib during cotreatment require further investigation.
doi:10.1016/s1879-5226(11)60004-3 fatcat:mbg55forkjfrpcma452sabbll4