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Cilengitide: an integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme Reardon DA; Nabors LB; Stupp R; Mikkelsen TExpert Opin Investig Drugs 2008[Aug]; 17 (8): 1225-35BACKGROUND: Glioblastoma multiforme (GBM), a highly invasive and vascular cancer, responds poorly to conventional cytotoxic therapy. Integrins, widely expressed in GBM and tumor vasculature, mediate cell survival, migration and angiogenesis. Cilengitide is a potent alphavbeta3 and alphavbeta5 integrin inhibitor. OBJECTIVE: To summarize the preclinical and clinical experience with cilengitide for GBM. METHODS: Preclinical studies and clinical trials evaluating cilengitide for GBM were reviewed. RESULTS/CONCLUSIONS: Cilengitide is active and synergizes with external beam radiotherapy in preclinical GBM models. In clinical trials for recurrent GBM, single-agent cilengitide has antitumor benefits and minimal toxicity. Among newly diagnosed GBM patients, single-arm studies incorporating cilengitide into standard external beam radiotherapy/temozolomide have shown encouraging activity with no increased toxicity and have led to a planned randomized Phase III trial.|Animals[MESH]|Antineoplastic Agents/administration & dosage/adverse effects/chemistry/*therapeutic use[MESH]|Central Nervous System Neoplasms/diagnosis/*drug therapy[MESH]|Clinical Trials as Topic[MESH]|Drug Evaluation, Preclinical[MESH]|Glioblastoma/diagnosis/*drug therapy[MESH]|Humans[MESH]|Integrins/*metabolism[MESH]|Models, Molecular[MESH]|Oligopeptides/administration & dosage/adverse effects/chemistry/*therapeutic use[MESH]|Protein Binding[MESH]|Snake Venoms/administration & dosage/adverse effects/chemistry/*therapeutic use[MESH]|Treatment Outcome[MESH] |
