Pharmacokinetics evaluation of nimotuzumab in combination with doxorubicin and cyclophosphamide in patients with advanced breast cancer

EGFr (Epidermal growth factor receptor) overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb (monoclonal antibody) that...

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Detalles Bibliográficos
Autores: Rodriguez-Vera, Leyanis, Fernández-Sanchez, Eduardo, Soriano, Jorge L., Batista, Noide, Lima, Maité, Gonzalez, Joaquín, Garcia, Robin, Viada, Carmen, Peraire i Guitart, Concepció, Colom Codina, Helena, Ramos-Suzarte, Mayra
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/69138
Acceso en línea:https://hdl.handle.net/2445/69138
Access Level:acceso abierto
Palabra clave:Càncer de mama
Anticossos monoclonals
Farmacocinètica
Breast cancer
Monoclonal antibodies
Pharmacokinetics
Descripción
Sumario:EGFr (Epidermal growth factor receptor) overexpression has been detected in many tumors of epithelial origin, specifically in breast cancer and it is often associated with tumor growth advantages and poor prognosis. The nimotuzumab is a genetically engineered humanized MAb (monoclonal antibody) that recognizes an epitope located in the extracellular domain of human EGFr. The aim of this study was to assess the pharmacokinetics of nimotuzumab in patients with locally advanced breast cancer who are receiving neoadyuvant therapy combined with the AC chemotherapy regimen (i.e., 60 mg/m2 of Doxorubicin and 600 mg/m2 of Cyclophosphamide in 4 cycles every 21 days). A single center, non-controlled, open Phase I clinical trial, with histopathological diagnosis of locally advanced stage III breast cancer, was conducted in 12 female patients. Three patients were enrolled at each of the following fixed dose levels: 50, 100, 200 and 400 mg/week. Multiple intermittent short-term intravenous infusions of nimotuzumab were administered weekly, except on weeks 1 and 10, when blood samples were drawn for pharmacokinetic assessments. Nimotuzumab showed dose-dependent kinetics. No anti-idiotypic response against nimotuzumab was detected in blood samples of participants. There was not interaction between the administration of nimotuzumab and chemotherapy at the dose levels studied. The optimal biological doses ranging were estimated to be 200 mg/weekly to 400 mg/weekly.