TY - JOUR
T1 - Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer
T2 - Scientific rationale and study design
AU - Beekman, Kathleen W.
AU - Colevas, A. Dimitrios
AU - Cooney, Kathleen
AU - DiPaola, Robert
AU - Dunn, Rodney L.
AU - Gross, Mitchell
AU - Keller, Evan T.
AU - Pienta, Kenneth J.
AU - Ryan, Charles J.
AU - Smith, David
AU - Hussain, Maha
N1 - Funding Information:
Grant support was provided by Cancer Therapy Evaluation Program, 5 P30 CA46592, Specialized Programs of Research Excellence P50CA69568, National Cancer Institute Grant P01 CA093900, and Merck KGaA, Darmstadt, Germany.
PY - 2006/3
Y1 - 2006/3
N2 - 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 αvβ3 and αvβ5 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 αvβ3- and αvβ5-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.
AB - 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 αvβ3 and αvβ5 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 αvβ3- and αvβ5-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.
KW - Angiogenesis
KW - EMD121974
KW - Hormone-refractory disease
KW - NSC 707544
KW - Prostate-specific antigen
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UR - http://www.scopus.com/inward/citedby.url?scp=33646859981&partnerID=8YFLogxK
U2 - 10.3816/CGC.2006.n.012
DO - 10.3816/CGC.2006.n.012
M3 - Article
C2 - 16729916
AN - SCOPUS:33646859981
SN - 1558-7673
VL - 4
SP - 299
EP - 302
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 4
ER -