title: Pharmacokinetic and pharmacodynamic evaluation of panitumumab in the treatment of colorectal cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Medical Oncology , The Queen Elizabeth Hospital , Woodville , 5011 , SA , Australia.
authors.forename: Louisa
authors.initials: L
authors.lastname: Lo
authors.affiliation: a Department of Medical Oncology , The Queen Elizabeth Hospital , Woodville , 5011 , SA , Australia.
authors.forename: Dainik
authors.initials: D
authors.lastname: Patel
authors.affiliation: a Department of Medical Oncology , The Queen Elizabeth Hospital , Woodville , 5011 , SA , Australia.|b School of Medicine , University of Adelaide , Adelaide , 5000 , SA , Australia.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Townsend
authors.affiliation: a Department of Medical Oncology , The Queen Elizabeth Hospital , Woodville , 5011 , SA , Australia.|b School of Medicine , University of Adelaide , Adelaide , 5000 , SA , Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Price
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000068818:Cetuximab / Q000008:administration & dosage / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D058990:Molecular Targeted Therapy; D000077544:Panitumumab; D018579:Patient Selection; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab; D000068818:Cetuximab
keywords: colorectal cancer; panitumumab; pharmacokinetics; resistance