Relationship between epidermal growth factor receptor gene mutations and the severity of adverse events by gefitinib in patients with advanced non-small cell lung cancer

Lung Cancer. 2006 Apr;52(1):99-103. doi: 10.1016/j.lungcan.2005.12.004. Epub 2006 Feb 28.

Abstract

Purpose: Recent reports have demonstrated that mutation of epidermal growth factor receptor (EGFR) gene is predictive factor for tumor responsiveness to gefitinib suggesting the importance of EGFR status for the treatment of the patients with non-small cell lung cancer (NSCLC). However, the relationship between EGFR mutation and adverse events of gefitinib is still unknown. The aim of this study was to evaluate its correlation.

Patients and methods: Twenty-six tumor samples from Japanese NSCLC patients who received gefitinib in Okayama University Hospital between November 2000 and October 2004 were examined exons 18-21 of EGFR using direct sequence method. We retrospectively reviewed the clinical records and compared EGFR mutation status with adverse events during gefitinib treatment.

Results: Of all 26 patients, EGFR mutation (exon 19 in-frame deletion, 6; exon 21 L858R, 5), were detected in 11 patients (42.3%). The principal adverse event was skin rash (89%), diarrhea (39%), and liver injury (39%). Grade 3 or more adverse events were not common. EGFR mutation status was correlated with neither its frequency nor severity of adverse events during gefitinib treatment including skin rash, diarrhea, liver injury, and interstitial lung disease. As expected, objective response rate of those with EGFR mutations was significantly higher than those without EGFR mutations (78% versus 21%, P<0.001).

Conclusion: Our study did not demonstrate the presence of close relationships between EGFR mutation status and adverse events during gefitinib treatment.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Chemical and Drug Induced Liver Injury
  • Diarrhea / chemically induced
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Exanthema / chemically induced
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Prognosis
  • Quinazolines / adverse effects*
  • Retrospective Studies

Substances

  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib