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Pharmacokinetics of gefitinib predicts antitumor activity for advanced non-small cell lung cancer.


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タイトル: Pharmacokinetics of gefitinib predicts antitumor activity for advanced non-small cell lung cancer.
著者: Nakamura, Yoichi / Sano, Kazumi / Soda, Hiroshi / Takatani, Hiroshi / Fukuda, Minoru / Nagashima, Seiji / Hayashi, Tomayoshi / Oka, Mikio / Tsukamoto, Kazuhiro / Kohno, Shigeru
発行日: 2010年 9月
出版者: the International Association for the Study of Lung Cancer
引用: Journal of thoracic oncology, 5(9), pp.1404-1409; 2010
抄録: INTRODUCTION: We assessed the relationship between the plasma concentration of gefitinib and its efficacy in Japanese patients with advanced non-small cell lung cancer (NSCLC). METHODS: Plasma trough levels of gefitinib were measured on days 3 (D3) and 8 (D8) by high-performance liquid chromatography in 44 patients with advanced NSCLC treated with 250 mg gefitinib daily. Eligibility criteria included performance status < or =3, age < or = 80 years, and stages IIIB-IV cancer. Epidermal growth factor receptor mutations in 23 patients were analyzed retrospectively. RESULTS: The median plasma gefitinib values were 662 ng/ml on D3 and 1064 ng/ml on D8, and the D8/D3 ratio was 1.587. The median progression-free survival (PFS) was 71 days, and the median overall survival was 224 days. Adenocarcinoma, never smoking, and high D8/D3 ratio were associated with better PFS. Multivariate analysis showed that PFS was associated with never smoking and high D8/D3 ratio. Never-smokers with a high D8/D3 ratio showed the best PFS. Overall survival was not associated with the D8/D3 ratio. Epidermal growth factor receptor mutation analysis of 23 patients showed that 15 patients had exon 19 deletion and/or exon 21 point mutation. Median PFS was similar between mutation-positive and mutation-negative individuals in the high D8/D3 group, whereas mutation-negative individuals in the low D8/D3 group showed the worst median PFS. CONCLUSIONS: A high D8/D3 ratio was independently associated with better PFS in patients with NSCLC treated with gefitinib. Our findings suggest that the pharmacokinetics of gefitinib may be involved in its antitumor activity.
キーワード: Chemotherapy / EGFR mutation / Gefitinib / Non-small cell lung cancer / Pharmacokinetics
URI: http://hdl.handle.net/10069/25919
ISSN: 15560864
DOI: 10.1097/JTO.0b013e3181e59a7b
PubMed ID: 20651613
権利: © 2010 by the International Association for the Study of Lung Cancer. / This is a non-final version of an article published in final form in Journal of thoracic oncology, 5(9), pp.1404-1409; 2010.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:030 学術雑誌論文

引用URI : http://hdl.handle.net/10069/25919

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