Efficacy of antiangiogenic therapy with TNP-470 in superficial and invasive bladder cancer models in mice

Objectives. To evaluate the efficacy of antiangiogenic therapy with O-(chlo racetyl-carbamoyl) fumagillol (TNP-470) in a superficial and an invasive bl adder cancer model in mice. The control of recurrent superficial and metast atic bladder cancer constitutes a major problem in urologic practice. Altho ugh the established therapies for these cases (immunotherapy, chemotherapy, and radiation therapy) have improved during the previous decades, further improvement and the reduction of existing side effects are needed. The inhi bition of angiogenesis represents a new concept in cancer therapy. Methods. We evaluated the in vitro effect of TNP-470 on the proliferation o f bovine capillary endothelial cells (BCE), the superficial transitional ce ll carcinoma (TCC) cell line (KK-47), and the invasive TCC cell line (MGH-U 1). To evaluate the in vivo effect of TNP-470 on the growth of advanced TCC s, both cell lines were injected subcutaneously into SCID mice. When tumors grew to a size of 100 to 200 mm(3), therapy either with TNP-470 or phospha te-buffered saline was initiated. Results. TNP-470 strongly inhibited endothelial cell proliferation in vitro . The in vitro proliferation of both bladder carcinoma cell lines was also inhibited by TNP-470. However, the doses inhibitory to bladder carcinoma ce lls were 100-fold higher than the doses that were effective in the inhibiti on of endothelial cell proliferation. In vivo, TNP-470 significantly inhibi ted the growth of advanced KK-47 (67%) and MGH-U1 (68%) tumors in SCID mice . Conclusions. Our results indicate that antiangiogenic therapy with TNP-470 is equally effective in advanced superficial and invasive bladder carcinoma models in mice. When our results are taken together with the reports of ot her laboratories, TNP-470 appears to be a promising candidate as a tumor su ppressor in superficial and invasive bladder cancer. UROLOGY 56: 521-526, 2 000. (C) 2000, Elsevier Science Inc.