Clinical Pharmacokinetics and Pharmacodynamics of the Epidermal Growth Factor Receptor Inhibitor Panitumumab in the Treatment of Colorectal Cancer

Clin Pharmacokinet. 2018 Apr;57(4):455-473. doi: 10.1007/s40262-017-0590-9.

Abstract

Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mCRC. Panitumumab is used in different lines of therapy in combination with chemotherapy, and as monotherapy for the treatment of wild-type (WT) RAS mCRC. It is administered as an intravenous infusion of 6 mg/kg every 2 weeks and has a t ½ of approximately 7.5 days. Elimination takes place via two different mechanisms, and immunogenicity rates are low. Only RAS mutations have been confirmed as a negative predictor of efficacy with anti-EGFR antibodies. Panitumumab is generally well tolerated and has a manageable toxicity profile, despite a very high prevalence of dermatologic side effects. This article presents an overview of the clinical pharmacokinetics and pharmacodynamics of panitumumab, including a description of the studies that led to its approval in the different lines of therapy of mCRC.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / pharmacokinetics*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / enzymology
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Drug Administration Schedule
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Genes, ras
  • Humans
  • Infusions, Intravenous
  • Mutation
  • Panitumumab / administration & dosage*
  • Panitumumab / adverse effects
  • Panitumumab / pharmacokinetics*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Panitumumab
  • EGFR protein, human
  • ErbB Receptors