Clinical trial with escalating doses of the antiepidermal growth factor receptor humanized monoclonal antibody EMD 72 000 in patients with advanced squamous cell carcinoma of the larynx and hypopharynx

In this open uncontrolled phase I study, nine patients with stage III and IV squamous cell carcinoma of the head and neck (SCCHN) were treated with five administrations of the humanized antiepidermal growth factor receptor monoclonal antibody EMD 72 000 in three consecutive ascending dose groups. Loading doses of 100 mg (group I), 200 mg (group II), and 400 mg (group III) were followed by four weekly maintenance doses of half the loading doses, i.e. 50, 100, and 200 mg, respectively. Two EMD 72 000 administrations were scheduled before and thr ec after surgery. The objectives of this trial were (a) to investigate the safety and toxicity of multiple EMD 72 000 doses, (b) to determine the cumulative maximum tolerated dose of EMD 72 000 at dosages between 300 mg and 1200 mg, and (c) to determine the serum pharmacokinetics of EMD 72 000. In total, 102 adverse events (AEs) were reported: five of toxicity grade 3, 18 of toxicity grade 2, 66 of toxicity grade 1, and 38 of toxicity grade 0. All AEs of toxicity grade 3 were considered to be not or remotely related to EMD 72 000. The most frequent study drug-related AEs were fever and a transient elevation of liver enzymes. In all patients, the time to roach peak serum concentrations (t(max)) was within 1-3 h of the start of each EMD 72 000 infusion. Average peak serum concentrations (C,,,,) after correction for dosage appeared to be dose-independent, whereas the half-life (t(1/2)) showed dose dependency. In conclusion, EMD 72 000 was very well tolerated in patients with advanced stage SCCHN. The pharmacokinetic data from this trial suggest the feasibility of conducting future studies with weekly doses of 200 mg EMD 72 000.