Two randomized trials demonstrated an improvement in survival with 
docetaxel-based chemotherapy for patients with metastatic, androgen-independent 
prostate disease. However, the effect of current therapy is suboptimal in that 
it is complicated by toxicities and has no curative potential. Cilengitide 
(EMD121974; NSC 707544), is a potent selective alphavbeta3 and alphavbeta5 
integrin antagonist. Integrins are cell surface receptors that mediate a variety 
of cell activities including endothelial cell proliferation and migration. 
Blocking the ligation of integrins by antagonists promotes apoptosis of 
proliferative angiogenic cells, thereby suspending new blood vessel formation, 
which is essential for the growth of malignant disease. In prostate cancer 
specifically, integrins are known to be involved in metastases with differential 
expression on tumor cells. Tumors and vascular endothelial cells produce 
factors, such as vascular endothelial growth factor and basic fibroblast growth 
factor, that promote neovascularization, which has been implicated in prostate 
cancer progression. Cilengitide has been shown to inhibit alphavbeta3- and 
alphavbeta5-mediated cell adhesion and block in vitro endothelial cell 
migration. In vivo experiments demonstrated that cilengitide inhibited 
cytokine-induced basic fibroblast growth factor- and vascular endothelial growth 
factor-mediated angiogenesis in a dose-dependent manner. Cilengitide also 
inhibited tumor growth in various in vivo systems. Two Cancer Therapy Evaluation 
Program-sponsored, multicenter, phase II trials are designed to evaluate the 
safety and efficacy of this agent in patients with androgen-independent prostate 
cancer. National Cancer Institute trial 6735 is evaluating cilengitide at 2000 
mg in patients with nonmetastatic androgen-independent prostate cancer, and 
National Cancer Institute trial 6372 is evaluating 2 dose levels of cilengitide, 
500 mg or 2000 mg, intravenously twice weekly in patients with metastatic 
prostate cancer.