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Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer

Tomohiro Suzumura1, Tatsuo Kimura, Shinzoh Kudoh

  • 1Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.

BMC Cancer
|December 5, 2012
PubMed
Abstract

Insights

Reduced CYP2D6 enzyme activity increases the risk of severe rash in patients treated with gefitinib. This finding highlights the importance of CYP2D6 phenotypes in predicting gefitinib-related adverse events.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Drug Metabolism

Background:

  • Erlotinib and gefitinib are EGFR inhibitors with known adverse events like rash, liver dysfunction, and diarrhea.
  • Cytochrome P450 (CYP) 2D6 metabolizes gefitinib but not erlotinib, suggesting a role for CYP2D6 phenotypes in differential adverse event profiles.

Purpose of the Study:

  • To investigate the association between CYP2D6 phenotypes and the occurrence of adverse events in patients receiving gefitinib or erlotinib therapy.

Main Methods:

  • Patient cohorts receiving gefitinib (n=232) or erlotinib (n=86) were analyzed for adverse event frequency.
  • CYP2D6 genotypes were determined using real-time PCR to categorize phenotypes into functional or reduced metabolic activity groups.
  • Odds ratios were calculated to assess the association between CYP2D6 activity, treatment type, and adverse events.

Main Results:

  • Reduced CYP2D6 function was linked to a higher risk of grade 2 or more rash in the gefitinib cohort (OR, 0.44; p=0.03).
  • No significant associations were found for diarrhea or liver dysfunction with CYP2D6 phenotypes in the gefitinib group.
  • No associations between CYP2D6 phenotypes and adverse events (rash, diarrhea, liver dysfunction) were observed in the erlotinib cohort.

Conclusions:

  • CYP2D6 phenotypes are a significant risk factor for developing rash in patients undergoing gefitinib treatment.
  • Reduced CYP2D6 activity is specifically associated with an increased frequency of rash in gefitinib-treated patients.

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