Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer
Open Access
- 4 April 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 94 (9), 1293-1299
- https://doi.org/10.1038/sj.bjc.6603083
Abstract
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.Keywords
This publication has 17 references indexed in Scilit:
- A phase I study of the humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with paclitaxel in patients with EGFR-positive advanced non-small-cell lung cancer (NSCLC)Annals Of Oncology, 2006
- Evaluation of Biologic End Points and Pharmacokinetics in Patients With Metastatic Breast Cancer After Treatment With Erlotinib, an Epidermal Growth Factor Receptor Tyrosine Kinase InhibitorJournal of Clinical Oncology, 2004
- Cetuximab, a Monoclonal Antibody Targeting the Epidermal Growth Factor Receptor, in Combination With Gemcitabine for Advanced Pancreatic Cancer: A Multicenter Phase II TrialJournal of Clinical Oncology, 2004
- Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigationCancer Treatment Reviews, 2004
- Phase I Study of the Humanized Antiepidermal Growth Factor Receptor Monoclonal Antibody EMD72000 in Patients With Advanced Solid Tumors That Express the Epidermal Growth Factor ReceptorJournal of Clinical Oncology, 2004
- Safety experience with IMC-C225, an anti-epidermal growth factor receptor antibodySeminars in Oncology, 2002
- Epidermal growth factor receptor-targeted therapy for pancreatic cancerSeminars in Oncology, 2002
- Global cancer statisticsCA: A Cancer Journal for Clinicians, 1999
- The epidermal growth factor receptor in human pancreatic cancerThe Journal of Pathology, 1992
- Humanization of a mouse monoclonal antibody by CDR–grafting: the importance of framework residues on loop conformationProtein Engineering, Design and Selection, 1991