[Preclinical and clinical results with the epidermal growth factor receptor inhibitor Gefitinib (ZD1839, Iressa)]

Minerva Med. 2004 Jun;95(3):233-41.
[Article in Italian]

Abstract

Since epidermal growth factor receptor (EGFR) is involved in tumor proliferation and angiogenesis, and in the mechanisms of resistance to chemo- and hormono-therapy, it represents a unique promising target for anticancer treatment. Gefinitib (Iressa, ZD1839), an inhibitor of the EGFR tyrosine kinase activity able to bind the intracellular domain of the receptor, is at present in clinical development. In preclinical models Gefitinib induced a dose-dependent response rate in tumor xenografts obtained from different human cancer cells lines. The expression of EGFR in the prior tumor did not appear to be a predictive marker for Gefitinib sensitivity. Furthermore, long-term drug use was well tolerated in mice without inducing resistance. However, tumors started to grow again after treatment interruption. Laboratory findings and in vivo data have prompted the evaluation of Gefitinib administered as a single oral daily dose alone or in combination with conventional anticancer treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor / drug effects
  • Clinical Trials as Topic
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / therapeutic use
  • Epidermal Growth Factor
  • ErbB Receptors / antagonists & inhibitors
  • Gefitinib
  • Humans
  • Mice
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Quinazolines
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib