Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer

摘要: The humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody matuzumab (formerly EMD 72000) is active against pancreatic cancer in preclinical studies. This phase I study assessed the safety and potential benefit of combined treatment with standard-dose gemcitabine. Three groups chemotherapy-naive advanced adenocarcinoma patients (n=17) received escalating doses (400 mg weekly, 800 mg biweekly, or weekly) gemcitabine (1000 mg m–2 weekly weeks 1–3 each 4-week cycle). Toxicity, antitumour activity, pharmacokinetic (PK) parameters, pharmacodynamic (PD) markers skin biopsies were evaluated. Severe treatment-related toxicities limited to grade 3 neutropenia (n=3), leucopenia (n=1), decreased white blood cell count (n=1). Common drug-related adverse events (grade 2=6, 1=7) fever 1=4). Matuzumab inhibited phosphorylated EGFR affected receptor-dependent signalling transduction; effects seen even lowest-dose group. Pharmacokinetic data consistent results monotherapy. Partial response (PR) stable disease occurred eight 12 evaluated (66.7%), three PRs among six group receiving weekly. biologically effective standard therapy appears well tolerated. combination feasible may have enhanced activity.