期刊
BRITISH JOURNAL OF CANCER
卷 94, 期 9, 页码 1293-1299出版社
SPRINGERNATURE
DOI: 10.1038/sj.bjc.6603083
关键词
EMD 72000; epidermal growth factor receptor; gemcitabine; matuzumab; pancreatic cancer
类别
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 (400mg weekly, 800mg biweekly, or 800mg weekly) and gemcitabine (1000mgm(-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 800mg weekly. Matuzumab in biologically effective doses with standard gemcitabine therapy appears well tolerated. The combination is feasible and may have enhanced activity.
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