Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective phase I/II trial, EMD 55,900, a murine monoclonal antibody (MAb) directed against EGF receptor, was administered at tumour recurrence to 16 patients previously treated with surgery, radiotherapy and chemotherapy for high grade supratentorial gliomas (11 glioblastomas, five anaplastic astrocytomas). Duration of treatment was planned for at least 4 weeks. The first 10 patients received 40 mg of MAb three times per week (median cumulative dose, 760 mg) and the last 6 patients received 200 mg three times per week (median cumulative dose, 2400 mg). Serum levels of EMD 55,900 were proportional to the injected dose. Repeated infusions of EMD 55,900 were well tolerated. In 13/16 patients, there were no adverse events. Among the 3 others, one had a grade IV neutropenia, one had a clinically asymptomatic hepatitis, and one had a skin rash. This last patient was the only one who had increased human antimouse antibodies (HAMA). After 4 weeks of therapy, 13 patients were evaluable for response. No measurable tumour regression was obtained with either schedule. 6 of the 13 patients (46%) showed evidence of progressive disease, while 7/13 (54%) had stable disease. All patients had progressive disease by 3 months. In this study, repeated infusions of EMD 55,900 were well tolerated but no therapeutic benefit was demonstrated.
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PMID:Multiple infusions of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (EMD 55,900) in patients with recurrent malignant gliomas. 869 67

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.
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PMID:Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer. 1662 65