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

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Yoichi NakamuraShigeru Kohno

Abstract

We assessed the relationship between the plasma concentration of gefitinib and its efficacy in Japanese patients with advanced non-small cell lung cancer (NSCLC). 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. 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...Continue Reading

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Citations

Jul 3, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Eiki IchiharaKatsuyuki Kiura
Dec 15, 2012·Clinical Medicine Insights. Oncology·Takuya ArakiKoujirou Yamamoto
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