Tiseo M, Bartolotti M, Gelsomino F, Bordi P
Medical Oncology Unit, University, Hospital of Parma, Parma, Italy.
Drug Des Devel Ther. 2010 May 25;4:81-98. doi: 10.2147/dddt.s6594.
Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease and their long-term prognosis remains poor. Epidermal growth factor receptor (EGFR)-targeted therapies, such as gefitinib, have been subjected to comprehensive clinical development. Several phase II and III trials evaluated the clinical efficacy of gefitinib as monotherapy in pretreated patients with advanced NSCLC, as well as both monotherapy and combined with chemotherapy in chemotherapy-naive patients. A phase III trial (ISEL) in heavily pretreated advanced NSCLC patients demonstrated some improvement in survival with gefitinib compared with placebo; however, the difference was not statistically significant within the overall population. A large phase III trial in pretreated patients (INTEREST) demonstrated the non-inferiority of gefitinib in comparison with docetaxel for overall survival, together with an improved quality of life and tolerability profiles. In a large phase III trial (IPASS) in Asian chemotherapy-naive, never or former light-smoker patients with adenocarcinoma, gefitinib was more effective than carboplatin-paclitaxel in prolonging progression-free survival, particularly in patients harboring EGFR gene mutations. Gefitinib was a generally well tolerated treatment, with skin rash and diarrhea being the most common treatment adverse events. As a result, gefitinib is expected to have a large impact on the management of patients with advanced NSCLC, in particular in EGFR mutated patients.
大多数非小细胞肺癌（NSCLC）患者就诊时已处于疾病晚期，其长期预后仍然较差。表皮生长因子受体（EGFR）靶向疗法，如吉非替尼，已经历了全面的临床开发。多项II期和III期试验评估了吉非替尼在经治晚期NSCLC患者中作为单一疗法的临床疗效，以及在初治患者中作为单一疗法和联合化疗的疗效。一项针对重度经治晚期NSCLC患者的III期试验（ISEL）表明，与安慰剂相比，吉非替尼可使生存期有所改善；然而，在总体人群中，这种差异无统计学意义。一项针对经治患者的大型III期试验（INTEREST）表明，在总生存期方面，吉非替尼不劣于多西他赛，同时生活质量和耐受性也有所改善。在一项针对亚洲初治、从不吸烟或曾经轻度吸烟的腺癌患者的大型III期试验（IPASS）中，吉非替尼在延长无进展生存期方面比卡铂-紫杉醇更有效，尤其是在携带EGFR基因突变的患者中。吉非替尼是一种耐受性普遍良好的治疗方法，皮疹和腹泻是最常见的治疗不良事件。因此，吉非替尼有望对晚期NSCLC患者的治疗产生重大影响，特别是对EGFR突变患者。
