Ranson M, Wardell S
Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester, UK.
J Clin Pharm Ther. 2004 Apr;29(2):95-103. doi: 10.1111/j.1365-2710.2004.00543.x.
Traditional cytotoxic anticancer therapies do not differentiate between tumour and host cells, and research efforts have been focused on finding new agents that target tumour tissue. Gefitinib ('Iressa', ZD1839) is an orally active epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal pathways implicated in solid tumour growth and metastasis. In phase II trials, gefitinib 250 mg/day demonstrated efficacy in the control of advanced non-small-cell lung cancer (NSCLC) in patients who had undergone prior chemotherapy. Response rates were 18.4 and 11.8%, and disease control rates were 54.4 and 42.2%, at 250 mg/day in two multicentre trials - IDEAL 1 and 2. Gefitinib also caused rapid relief from the symptoms of NSCLC in approximately 40% of patients, while displaying a generally good tolerability profile that most commonly included mild, reversible gastrointestinal and skin adverse events. Gefitinib 250 mg/day has been approved for use in advanced, previously treated NSCLC in several countries including the USA, Japan and Australia. As a monotherapy and combination therapy, it is being investigated for the treatment of several common tumour types in addition to NSCLC. The pharmacokinetics of gefitinib have shown it to be suitable for once daily dosing, with a terminal half-life of approximately 48 h in patients with cancer. Steady-state exposure is achieved after 10 days dosing, and exposure is dose proportional up to 250 mg/day. Gefitinib is cleared principally by the biliary route and in part by metabolism. This review summarizes relevant data from studies of gefitinib that inform its clinical administration.
传统的细胞毒性抗癌疗法无法区分肿瘤细胞和宿主细胞，因此研究工作一直聚焦于寻找靶向肿瘤组织的新药物。吉非替尼（“易瑞沙”，ZD1839）是一种口服活性表皮生长因子受体酪氨酸激酶抑制剂，可阻断与实体瘤生长和转移相关的信号通路。在II期试验中，对于先前接受过化疗的患者，每天服用250毫克吉非替尼显示出对晚期非小细胞肺癌（NSCLC）的控制效果。在两项多中心试验——IDEAL 1和IDEAL 2中，每天服用250毫克吉非替尼的患者缓解率分别为18.4%和11.8%，疾病控制率分别为54.4%和42.2%。吉非替尼还使约40%的NSCLC患者症状迅速缓解，同时总体耐受性良好，最常见的不良反应为轻度、可逆的胃肠道和皮肤事件。在美国、日本和澳大利亚等多个国家，每天服用250毫克吉非替尼已被批准用于治疗晚期、先前接受过治疗的NSCLC。作为单一疗法和联合疗法，除NSCLC外，它还在被研究用于治疗几种常见的肿瘤类型。吉非替尼的药代动力学表明其适合每日一次给药，癌症患者的终末半衰期约为48小时。给药10天后达到稳态血药浓度，在每日剂量高达250毫克时血药浓度与剂量成正比。吉非替尼主要通过胆汁途径清除，部分通过代谢清除。本综述总结了吉非替尼研究中的相关数据，这些数据为其临床应用提供了参考。
