First-line gefitinib therapy for elderly patients with non-small cell lung cancer harboring EGFR mutation: Central Japan Lung Study Group 0901 |
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Authors: | Kosuke Takahashi Hiroshi Saito Yoshinori Hasegawa Masahiko Ando Masashi Yamamoto Eiji Kojima Yasuteru Sugino Tomoki Kimura Fumio Nomura Tomohiko Ogasawara Joe Shindoh Norio Yoshida Ryujiro Suzuki |
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Affiliation: | 1. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China 2. Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China 3. Zhejiang Beta Pharma Inc., Hangzhou, China 4. Beta Pharma Inc., New Haven, CT, USA
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Abstract: | Purpose Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Methods Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Results Plasma concentration of Icotinib reached peak at a median Tmax of 0.75–3.5 h after single dose and then declined with a mean t1/2β of 6.02–7.83 h. Over the dose range of 100–600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. Conclusion The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100–600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects. |
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