ArticleBMC cancer2012
Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Genetic Variants in theGenes · 2024Pooled it
- Pooled it
- Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.Medicine · 2018Pooled it
- CYP2D6 Genotype Phenotype Discordance Due to Drug-Drug Interaction.Clinical pharmacology and therapeutics · 2018Trial
- Scutellarein attenuates cancer cachexia-induced muscle atrophy via targeted inhibition of the JAK/STAT pathway.Journal of advanced research · 2026Article
- Therapeutic Drug Monitoring of Oral Targeted Anticancer Drugs: Achievements, Experiences, Challenges, and the Path Forward.Therapeutic drug monitoring · 2025Review
- Influence of genetic polymorphisms on gefitinib pharmacokinetics and adverse drug reactions in non-small cell lung cancer patients.Cancer metastasis reviews · 2025Review
- The Three Musketeers in Cancer Therapy: Pharmacokinetics, Pharmacodynamics and Personalised Approach.Journal of personalized medicine · 2025Review
- Gefitinib-Induced Severe Dermatological Adverse Reactions: A Case Report and Pharmacogenetic Profile.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Kinase Inhibitors FDA Approved 2018-2023: Drug Targets, Metabolic Pathways, and Drug-Induced Toxicities.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Article
- Role of epigenetics in OSCC: an understanding above genetics.Medical oncology (Northwood, London, England) · 2023Review
- CYP450 and drug efflux transporters polymorphism influence clinical outcomes of Thai osimertinib-treated non-small cell lung cancer patients.Frontiers in pharmacology · 2023Article
- CYP2D6 pharmacogenetics and phenoconversion in personalized medicine.Expert opinion on drug metabolism & toxicology · 2022Review
- Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers.Molecular cancer · 2022Review
- An investigation into possible interactions among four vascular epidermal growth factor receptor-tyrosine kinase inhibitors with gefitinib.Cancer chemotherapy and pharmacology · 2021Article
- Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450.Journal of personalized medicine · 2020Review
- Fatal toxic effects related to EGFR tyrosine kinase inhibitors based on 53 cohorts with 9,569 participants.Journal of thoracic disease · 2020Article
- Gene polymorphism of cytochrome P450 significantly affects lung cancer susceptibility.Cancer medicine · 2019Article
- Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology.Drug safety · 2019Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportions of adverse events compared to trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies.
methodsThe frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types.
resultsA total of 232 patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21-0.94; *p = 0.03), but not diarrhea ≥ grade 2 (OR, 0.49; 95% CI, 0.17-1.51; *p = 0.20) or liver dysfunction ≥ grade 2 (OR, 1.08; 95% CI, 0.52-2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54-6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21-7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20-5.07; *p = 0.93).
conclusionsThe frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.
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