Pharmacokinetics of Gefitinib Predicts Antitumor Activity for Advanced Non-small Cell Lung Cancer

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 <= 3, age <= 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 Mull D8/D3 ratio were associated with better PFS Multivariate analysis showed that HS 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 PI'S 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