ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, alone and in combination with radiation and chemotherapy as a new therapeutic strategy in non-small cell lung cancer

Semin Oncol. 2002 Feb;29(1 Suppl 4):37-46. doi: 10.1053/sonc.2002.31521.

Abstract

The epidermal growth factor receptor is overexpressed in a majority of non-small cell lung cancers and has been associated with a poor prognosis. Preclinical studies have shown that ZD1839, an oral anilinoquinazoline, targets the epidermal growth factor receptor-associated tyrosine kinase, reversibly inhibiting critical downstream signaling and resulting in cancer cell growth arrest. Potent antitumor effects have been observed in human lung tumor xenograft models. Preclinical studies have shown additive to synergistic effects when ZD1839 is combined with radiation or chemotherapy in colon, head and neck, and non-small cell lung cancers. Phase I clinical trials have shown modest dose-related toxicity, and antitumor activity has been reported in a variety of malignancies including lung cancer. Future studies will certainly combine ZD1839 with chemotherapy or radiation. ZD1839 also may be effective as a chemoprevention agent because premalignant lesions often overexpress epidermal growth factor receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Cycle / drug effects
  • Chemoprevention
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease Models, Animal
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / drug effects
  • ErbB Receptors / metabolism*
  • Gefitinib
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / radiotherapy
  • Quinazolines / administration & dosage
  • Quinazolines / pharmacology*
  • Signal Transduction / drug effects
  • Transplantation, Heterologous
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib