Gefitinib
Gefitinib
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DOI：
10.2165/00003495-200262150-00008
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发表时间：
2002-01-01
期刊：
影响因子：
11.5
通讯作者：
Faulds, D
中科院分区：
文献类型：
--
作者：
Culy, CR;Faulds, D
吉非替尼（ZD 1839）是一种口服活性的表皮生长因子受体酪氨酸激酶选择性抑制剂，这种酶调节与癌细胞增殖和存活有关的细胞内信号通路。在人非小细胞肺癌（NSCLC）细胞系和异种移植物中，吉非替尼剂量依赖性地抑制细胞增殖和肿瘤生长，吉非替尼具有口服生物利用度，并通过细胞色素P450 3A 4途径清除。在接受吉非替尼的患者中（50至700 mg/天），在I期试验中，在7至10天内达到稳态血药浓度。在一次或两次化疗失败的晚期NSCLC患者中，在一项双盲试验（n = 210）中，吉非替尼250或500 mg每日一次在约19%的患者中诱导了客观反应。一项包括216例既往化疗失败的NSCLC患者的盲法试验，吉非替尼250或500 mg每日1次分别在11.8%和8.8%的患者中诱导了客观缓解;大约有40%的人表现出疾病的改善-吉非替尼的耐受性一般良好，最常见的不良反应是轻微的皮疹和腹泻。
Gefitinib (ZD1839) is an orally active selective inhibitor of epidermal growth factor receptor tyrosine kinase, an enzyme that regulates intracellular signalling pathways implicated in the proliferation and survival of cancer cells.In human non-small cell lung cancer (NSCLC) cell lines and xenografts, gefitinib dose-dependently inhibited cellular proliferation and tumour growth, and potentiated the cytotoxic effects of chemotherapy and/or radiation.Gefitinib is orally bioavailable and is cleared via the cytochrome P450 3A4 pathway. In patients receiving gefitinib (50 to 700 mg/day) in phase I trials, steady-state plasma concentration was reached in 7 to 10 days.In patients with advanced NSCLC who had failed one or two prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in approximate to 19% of patients in a double-blind trial (n = 210).In another double-blind trial including 216 patients with NSCLC who had failed two or more prior chemotherapies, gefitinib 250 or 500mg once daily induced an objective response in 11.8 and 8.8% of patients, respectively; approximate to40% showed an improvement in disease-related symptoms.Gefitinib was generally well tolerated and the most common adverse events were mild skin rashes and diarrhoea.