期刊
CLINICAL GENITOURINARY CANCER
卷 4, 期 4, 页码 299-302出版社
CIG MEDIA GROUP, LP
DOI: 10.3816/CGC.2006.n.012
关键词
angiogenesis; EMD121974; hormone-refractory disease; NSC 707544; prostate-specific antigen
资金
- NCI NIH HHS [P01 CA093900, 5 P30 CA46592, P50CA69568] Funding Source: Medline
Two randomized trials demonstrated an improvement in survival with docetaxel-based chemotherapy for patients with metastatic, androgenindependent prostate disease. However, the effect of current therapy is suboptimal in that it is complicated by toxicities and has no curative potential. Cilengiticle (EMD121974; NSC 707544), is a potent selective alpha nu beta 3 and alpha nu beta 5 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 ctvp3- and avp5-mediated cell adhesion and block in vitro enclothelial cell migration. In vivo experiments demonstrated that cilengitide inhibited cytoki ne- induced basic fibroblast growth factor- and vascular enclothelial growth factor-mediated angiogenesis in a dose-dependent manner. Cilengiticle also inhibited tumor growth in various in vivo systems. Two Cancer Therapy Evaluation Program-sponsored, multicenter, phase 11 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 cilengiticle, 500 mg or 2000 mg, intravenously twice weekly in patients with metastatic prostate cancer.
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