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A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies.
- Source :
-
Investigational new drugs [Invest New Drugs] 2011 Oct; Vol. 29 (5), pp. 996-1003. Date of Electronic Publication: 2010 May 08. - Publication Year :
- 2011
-
Abstract
- Purpose: Nimotuzumab is a humanized monoclonal antibody which inhibits the ligand-dependent activation of epidermal growth factor receptor (EGFR). We conducted a phase I trial to assess the pharmacodynamic (PD) effects of escalating doses of nimotuzumab administered alone in patients with advanced solid cancers patients.<br />Experimental Design: Patients were treated with escalating doses of weekly intravenous nimotuzumab at doses ranging between 100 and 800 mg. Tumor and skin biopsies were done before start of treatment and repeated 3 weeks after to assess immunohistochemical expression of EGFR and its downstream components.<br />Results: Seventeen patients were enrolled, including 1 patient never treated. Although 1 dose-limiting-toxicity (DLT) was observed at 100 mg (grade 3 fatigue), nimotuzumab dose was escalated to 800 mg with no other DLT. No grade 4 toxicity was observed. Only 3 patients developed a grade 1 acneiform rash (18.7%). One patient achieved a partial response (6.2%) and 8 patients had stable disease (50.0%). The median TTP was 2.4 months. No significant changes in EGFR, AKT, ERK and Ki67 immuno-stainings were observed between pre- and on-treatment tumor or skin biopsies.<br />Conclusion: Nimotuzumab could be safety administered up to 800 mg with manageable toxicity. No relationships were found between pharmacodynamic effects on EGFR downstream signaling pathways and drug efficacy or toxicity.
- Subjects :
- Aged
Antibodies, Monoclonal adverse effects
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal, Humanized adverse effects
Antibodies, Monoclonal, Humanized pharmacology
Antineoplastic Agents adverse effects
Antineoplastic Agents pharmacology
Biomarkers, Tumor metabolism
Disease Progression
Dose-Response Relationship, Drug
ErbB Receptors metabolism
Female
Humans
Kaplan-Meier Estimate
Ligands
Male
Middle Aged
Neoplasm Staging
Neoplasms enzymology
Time Factors
Treatment Outcome
Antibodies, Monoclonal therapeutic use
Antibodies, Monoclonal, Humanized therapeutic use
Antineoplastic Agents therapeutic use
ErbB Receptors antagonists & inhibitors
Neoplasms drug therapy
Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-0646
- Volume :
- 29
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Investigational new drugs
- Publication Type :
- Academic Journal
- Accession number :
- 20454832
- Full Text :
- https://doi.org/10.1007/s10637-010-9444-0