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Type: Journal article
Title: Pharmacokinetic and pharmacodynamic evaluation of panitumumab in the treatment of colorectal cancer
Author: Lo, L.
Patel, D.
Townsend, A.
Price, T.
Citation: Expert Opinion on Drug Metabolism & Toxicology, 2015; 11(12):1907-1924
Publisher: Taylor & Francis
Issue Date: 2015
ISSN: 1742-5255
Statement of
Louisa Lo, Dainik Patel, Amanda R Townsend, Timothy J Price
Abstract: Introduction: Integration of targeted therapy and additional chemotherapy options has improved median overall survival (OS) in patients with unresectable metastatic colorectal cancer (mCRC). Cetuximab and panitumumab are examples of targeted therapies, specifically against the epidermal growth factor receptor (EGFR). This review focuses on Panitumumab, a fully human IgG2 monoclonal antibody, which inhibits key oncogenic downstream cell signalling pathways. Panitumumab and cetuximab have improved tumour response rate, progression-free survival, and OS in mCRC patients in whom the RAS (Rat Sarcoma) gene is of Wild Type (WT) status. Areas covered: The EGFR signalling pathway and preclinical, Phase I and Phase II clinical studies on the pharmacokinetic, pharmacodynamic and safety evaluation of panitumumab are presented. Phase III studies utilising panitumumab in the first, second and third line setting in mCRC are also described. Expert opinion: Panitumumab exhibits excellent pharmacokinetics and pharmacodynamics by way of uncomplicated dosing, non-existent drug interactions, minimal infusion reactions and manageable side effects, making it a suitable target for combination treatments. However, innate and acquired resistances are still obstacles. To overcome this, experimented strategies are ongoing, particularly in patients with Her-2 and BRAF gene alterations. Novel biomarkers to improve patient selection and second-generation targeted antibodies are in development.
Keywords: Colorectal cancer; panitumumab; pharmacokinetics; resistance
Description: Published online: 16 Nov 2015
Rights: © Taylor & Francis. All rights reserved: reproduction in whole or in part not permitted
RMID: 0030039211
DOI: 10.1517/17425255.2015.1112787
Appears in Collections:Medicine publications

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