WEKO3
インデックスリンク
アイテム
Effects of pharmacokinetics-related genetic polymorphisms on the side effect profile of afatinib in patients with non-small cell lung cancer
https://gifu-pu.repo.nii.ac.jp/records/13721
https://gifu-pu.repo.nii.ac.jp/records/13721624aa97f-2e5c-43be-9a7d-21f0d13cdb99
| Item type | 研究室原著論文(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-03-04 | |||||
| タイトル | ||||||
| タイトル | Effects of pharmacokinetics-related genetic polymorphisms on the side effect profile of afatinib in patients with non-small cell lung cancer | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 抄録 | ||||||
| 値 | OBJECTIVES: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) represent the first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer. Afatinib is a second-generation EGFR-TKI with excellent therapeutic effects. However, severe diarrhea and skin disorders are observed at high frequencies, often leading to treatment interruption because of low quality of life (QOL). The relationship between individual variations and the onset of these side effects remains to be elucidated. This study aimed to reveal the association among these side effects, pharmacokinetics, and related genetic polymorphisms. MATERIALS AND METHODS: In total, 33 patients were recruited between July 2014 and June 2017. Afatinib plasma concentrations were measured at day 9 when the concentrations reached a steady state (early phase) and when the prescription dose was stable for more than 1 month (stable phase). We analyzed single nucleotide polymorphisms in the genes ATP-binding cassette sub-family B member 1 (ABCB1), ABCG2, and flavin-containing monooxygenase 3. RESULTS: The incidences of both diarrhea and acneiform eruption were greater than 80%. Afatinib plasma concentration and the severity of diarrhea in the early phase were correlated. Pharmacokinetics-related genetic polymorphisms influenced the severity of diarrhea. Particularly, the afatinib plasma concentration was higher and diarrhea was more severe in patients carrying the A allele of ABCG2 C421A. Onset of side effects, genetic polymorphisms, and diarrhea in the maintenance phase or acneiform eruption in the early or maintenance phases were not correlated. The severity of diarrhea is influenced by drug plasma concentrations in the early phase and genetic polymorphisms related to afatinib pharmacokinetics. CONCLUSION: Particular genetic polymorphisms can be screened before afatinib administration and the dose adapted to individual patients can be controlled, leading to reduced side effects, improved QOL, and better patient compliance to maintain the therapeutic effects. |
|||||
| 書誌情報 |
en : Lung Cancer 巻 134, p. 1-6, 発行日 2019 |
|||||
| DOI | ||||||
| 値 | 10.1016/j.lungcan.2019.05.013 | |||||
