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.

Angiogenesis inhibitor, Cilengitide (EMD 121974), Integrins, Pharmacology, Phase I clinical trial
dx.doi.org/10.1016/S0959-8049(03)00057-1, hdl.handle.net/1765/63567
European Journal of Cancer
Department of Medical Oncology

Eskens, F.A.L.M, Dumez, H, Hoekstra, R, Perschl, A, Brindley, C, Böttcher, S, … van Oosterom, A.T. (2003). 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. European Journal of Cancer, 39(7), 917–926. doi:10.1016/S0959-8049(03)00057-1