Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Graeven, U. et al.

Graeven, Kremer, Südhoff, Killing, Rojo, Weber, Tillner, Unal, Schmiegel,

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

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 matuzumab and standard-dose gemcitabine. Three groups of chemotherapy-naive advanced pancreatic adenocarcinoma patients (n=17) received escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly) and gemcitabine (1000 mg m(-2) weekly in weeks 1-3 of each 4-week cycle). Toxicity, antitumour activity, pharmacokinetic (PK) parameters, and pharmacodynamic (PD) markers in skin biopsies were evaluated. Severe treatment-related toxicities were limited to grade 3 neutropenia (n=3), leucopenia (n=1), and decreased white blood cell count (n=1). Common study drug-related adverse events were skin toxicities (grade 2=6, grade 1=7) and fever (grade 1=4). Matuzumab inhibited phosphorylated EGFR and affected receptor-dependent signalling and transduction; effects were seen even in the lowest-dose group. Pharmacokinetic data were consistent with results of matuzumab monotherapy. Partial response (PR) or stable disease occurred in eight of 12 evaluated patients (66.7%), with three PRs among six evaluated patients in the group receiving 800 mg weekly. Matuzumab in biologically effective doses with standard gemcitabine therapy appears well tolerated. The combination is feasible and may have enhanced activity.British Journal of Cancer (2006) 94, 1293-1299. doi:10.1038/sj.bjc.6603083 www.bjcancer.com Published online 4 April 2006.[1]

References

Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer. Graeven, U., Kremer, B., Südhoff, T., Killing, B., Rojo, F., Weber, D., Tillner, J., Unal, C., Schmiegel, W. Br. J. Cancer (2006) [Pubmed]

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