Gefitinib A Review of its Use in the Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer
Gefitinib A Review of its Use in the Treatment of Locally Advanced/Metastatic Non-Small Cell Lung Cancer
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DOI：
10.2165/10489100-000000000-00000
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发表时间：
2009-01-01
期刊：
影响因子：
11.5
通讯作者：
Scott, Lesley J.
中科院分区：
文献类型：
--
作者：
Sanford, Mark;Scott, Lesley J.
吉非替尼 (Iressa (TM)) 是一种表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂，可为局部晚期或转移性非小细胞肺癌 (NSCLC) 患者提供治疗，特别是那些携带 EGFR 突变的患者。在一项大型 III 期试验 (IPASS) 中，受试者为从未吸烟者或既往轻度吸烟者的亚洲腺癌初治患者，口服吉非替尼在延长无进展生存期 (PFS) 方面比卡铂加紫杉醇更有效。在预先指定的亚组分析中，EGFR 突变阳性状态与吉非替尼治疗的阳性反应相关。此外，一项针对未接受过化疗的非小细胞肺癌患者的试验（仅限于具有 EGFR 突变的患者）发现，吉非替尼接受者的 PFS 显着长于卡铂加紫杉醇接受者。在未经选择的既往治疗患者中进行的大型 III 期试验（INTEREST，V-15-32）中，吉非替尼接受者的总生存期 (OS) 不劣于多西他赛接受者，或没有显着差异。在一项针对既往治疗患者 (ISEL) 的安慰剂对照试验中，对亚洲患者和非吸烟者预先计划的亚组分析表明，在这些亚组中，吉非替尼延长了 OS，并且 EGFR 生物标志物预测对吉非替尼的阳性反应。吉非替尼还与未接受过化疗和既往接受过治疗的患者的生活质量 (QOL) 改善有关。在 EGFR 突变阳性患者中进行吉非替尼与厄洛替尼的头对头试验将有助于在该人群中确定吉非替尼与厄洛替尼的相对位置。还需要进一步的研究来确定与 EGFR 突变阳性患者对 EGFR 酪氨酸激酶抑制剂无反应相关的因素。吉非替尼是一种耐受性良好的治疗方法，皮疹和腹泻是最常见的治疗中出现的不良事件。间质性肺疾病（ILD）是一种与吉非替尼和其他癌症治疗相关的严重非小细胞肺癌合并症；在参与临床试验的吉非替尼接受者中，ILD 型事件的总体发生率约为 1%，并且在亚洲患者中更为常见。值得注意的是，与比较化疗方案相比，吉非替尼的血液学和神经学不良反应显着减少。吉非替尼单药治疗是治疗带有 EGFR 突变的局部晚期或转移性 NSCLC 患者的有效方法。
Gefitinib (Iressa (TM)) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that offers treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), in particular in those who are harbouring EGFR mutations. In a large phase III trial (IPASS) in chemotherapy-naive Asian patients with adenocarcinoma who were never smokers or former light smokers, oral gefitinib was more effective than carboplatin plus paclitaxel in prolonging progression-free survival (PFS). In a prespecified subgroup analysis, EGFR-mutation-positive status was associated with a positive response to gefitinib treatment. Furthermore, a trial in chemotherapy-naive patients with NSCLC that was restricted to those with EGFR mutations found that gefitinib recipients had significantly longer PFS than carboplatin plus paclitaxel recipients. In large phase III trials (INTEREST, V-15-32) in unselected, previously treated patients, the overall survival (OS) in gefitinib recipients was noninferior to, or not significantly different from, that of docetaxel recipients. In a placebo-controlled trial in previously treated patients (ISEL), pre-planned subgroup analyses in Asian patients and non-smokers showed that in these subgroups gefitinib prolonged OS, and that EGFR biomarkers predicted a positive response to gefitinib. Gefitinib was also associated with greater improvements in quality of life (QOL) in both chemotherapy-naive and previously treated patients. A head-to-head trial of gefitinib versus erlotinib in EGFR-mutation-positive patients would help position gefitinib relative to erlotinib in this population. Further research is also required to identify factors associated with non-response to EGFR-tyrosine-kinase inhibitors in EGFR-mutation-positive patients. Gefitinib was a generally well tolerated treatment, with rash and diarrhoea being the most common treatment-emergent adverse events. Interstitial lung disease (ILD) is a serious co-morbidity of NSCLC associated with gefitinib and other cancer treatments; ILD-type events occurred with an overall incidence of approximate to 1% in gefitinib recipients participating in clinical trials, and were more common in Asian patients. Notably, gefitinib was associated with significantly fewer haematological and neurological adverse effects than comparator chemotherapy regimens. Gefitinib as monotherapy is an effective treatment for patients with locally advanced or metastatic NSCLC with EGFR mutations.