Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of Cilengitide (EMD 121974), a novel inhibitor of the integrins αvβ3 and αvβ5 in patients with advanced solid tumours

• Published in: European journal of cancer (1990) Vol. 39; no. 7; pp. 917 - 926
• Main Authors: Eskens, F.A.L.M, Dumez, H, Hoekstra, R, Perschl, A, Brindley, C, Böttcher, S, Wynendaele, W, Drevs, J, Verweij, J, van Oosterom, A.T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-05-2003; Elsevier
• Subjects: Angiogenesis inhibitor; Antineoplastic agents; Biological and medical sciences; Chemotherapy; Cilengitide (EMD 121974); Integrins; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Pharmacology; Pharmacology. Drug treatments; Phase I clinical trial; Tumors; Pharmacology; Cilengitide (EMD 121974); Phase I clinical trial; Angiogenesis inhibitor; Integrins; Antineoplastic agent; Human; Solid tumor; Peptides; Maximal dose; Toxicity; Inlegrins; Treatment efficiency; Chemotherapy; Integrin; Phase I trial; Cilengitide; Advanced stage; Inhibitor; Pharmacokinetics; Therapeutic protocol
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(03)00057-1

A single-agent dose escalating phase I and pharmacokinetic study with Cilengitide, an inhibitor of the integrins αvβ3 and αvβ5, was performed to determine its safety and toxicity. Cilengitide was administered as a one-hour infusion twice weekly without interruption to patients with histologically- or cytologically-confirmed metastatic solid tumours. Plasma pharmacokinetics were determined at days 1 and 15. 37 patients were enrolled into the study. Dose levels studied were 30, 60, 120, 180, 240, 400, 600, 850, 1200, and 1600 mg/m2/infusion. There was no dose-limiting toxicity (DLT). Pharmacokinetics were dose-independent and time-invariant. Apparent terminal half-life ranged from 3 to 5 h. At 120 mg/m2/infusion, peak plasma concentrations were attained that optimally inhibited tumour growth in preclinical models. Cilengitide can be safely administered using a continuous twice-weekly infusion regimen. As DLT was not reached, future trials should explore Cilengitide at different doses.