Pharmacokinetics of gefitinib predicts antitumor activity for advanced non-small cell lung cancer
| Autor: | Minoru Fukuda, Hiroshi Takatani, Kazuhiro Tsukamoto, Shigeru Kohno, Seiji Nagashima, Yoichi Nakamura, Hiroshi Soda, Kazumi Sano, Mikio Oka, Tomayoshi Hayashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Oncology
Pulmonary and Respiratory Medicine Male medicine.medical_specialty Lung Neoplasms Antineoplastic Agents Adenocarcinoma Gefitinib Non-small cell lung cancer Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Humans Chemotherapy Pharmacokinetics Epidermal growth factor receptor Lung cancer Survival rate neoplasms Aged Neoplasm Staging Retrospective Studies Performance status biology business.industry Cancer Middle Aged medicine.disease respiratory tract diseases Survival Rate Treatment Outcome biology.protein Quinazolines Female EGFR mutation business medicine.drug |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 5(9):1404-1409 |
| ISSN: | 1556-0864 |
| Popis: | 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. Journal of thoracic oncology, 5(9), pp.1404-1409; 2010 |
| Databáze: | OpenAIRE |
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