Gefitinib

Drugs. 2002;62(15):2237-48; discussion 2249-50. doi: 10.2165/00003495-200262150-00008.

Abstract

Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells. In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation. Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days. In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in approximately 19% of patients in a double-blind trial (n = 210). In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; approximately 40% showed an improvement in disease-related symptoms. Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Biological Availability
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • ErbB Receptors / antagonists & inhibitors*
  • Gefitinib
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Quinazolines / adverse effects
  • Quinazolines / pharmacokinetics
  • Quinazolines / therapeutic use*
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib