Veronese Maria Luisa, Algazy Kenneth, Bearn Lisa, Eaby Beth, Alavi Jane, Evans Tracey, Stevenson James P, Shults Justine
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Cancer Invest. 2005;23(4):296-302. doi: 10.1081/cnv-61528.
Gefitinib (Iressa; AstraZeneca Pharmaceuticals, Wilmington, DE) is an oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with favorable toxicity and antitumor activity in pretreated patients with non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the toxicity and efficacy of gefitinib in patients with advanced NSCLC treated at our institution as part of an expanded access protocol; 112 patients with advanced NSCLC were entered. All patients had failed at least one previous chemotherapy regimen, or were not suitable for any systemic chemotherapy because of poor performance status (PS), or were ineligible for other clinical trials. Therapy consisted of gefitinib 250 mg orally once daily; 10.5% (95% CI 5.3-17.9%) of patients achieved partial/minimal response (PR/MR) and 29.5% (95% CI 21.0-39.2%) had stable disease (SD), resulting in a disease control rate (PR/MR+SD) of 40% (95% CI 31-50%). The median duration of treatment for all patients was 12 weeks (range 2-116 weeks) and for patients achieving disease control 28 weeks (range 8-116). Nine patients received gefitinib for more than 1 year. Median survival was 30 weeks. Symptoms were improved in 36% of evaluable patients, and 64% of patients who achieved disease control experienced improvement of their disease related symptoms. Adverse events were generally mild and consisted mostly of skin rash (48%) and diarrhea (38%). A statistically significant association was observed between disease control and skin rash (p = < 0.001), nonsmoking status (p = 0.048), and symptom improvement (p = 0.001). The disease control rate was not statistically associated with histology, PS, gender, or number of prior treatments. In addition, longer survival was significantly associated with skin rash (p = < 0.001) and symptom improvement (p = < 0.001). Gefitinib demonstrated relevant clinical activity and a favorable toxicity profile in pretreated patients with advanced NSCLC. The development of toxicity was associated with a favorable response. In addition, a history of never having smoked seems to predict a higher efficacy of gefitinib.
吉非替尼（易瑞沙；阿斯利康制药公司，特拉华州威尔明顿）是一种口服表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），对经治的非小细胞肺癌（NSCLC）患者具有良好的毒性和抗肿瘤活性。本研究的目的是评估作为扩大准入方案一部分在我们机构接受治疗的晚期NSCLC患者中吉非替尼的毒性和疗效；纳入了112例晚期NSCLC患者。所有患者既往至少一种化疗方案治疗失败，或因身体状况差（PS）不适合任何全身化疗，或不符合其他临床试验的入组标准。治疗方案为口服吉非替尼250mg，每日一次；10.5%（95%CI 5.3 - 17.9%）的患者达到部分/微小缓解（PR/MR），29.5%（95%CI 21.0 - 39.2%）病情稳定（SD），疾病控制率（PR/MR + SD）为40%（95%CI 31 - 50%）。所有患者的中位治疗持续时间为12周（范围2 - 116周），疾病得到控制的患者为28周（范围8 - 116周）。9例患者接受吉非替尼治疗超过1年。中位生存期为30周。36%的可评估患者症状改善，64%疾病得到控制的患者疾病相关症状有所改善。不良事件一般较轻，主要包括皮疹（48%）和腹泻（38%）。在疾病控制与皮疹（p = < 0.001）、不吸烟状态（p = 0.048）和症状改善（p = 0.001）之间观察到有统计学意义的关联。疾病控制率与组织学、PS、性别或既往治疗次数无统计学关联。此外，更长的生存期与皮疹（p = < 0.001）和症状改善（p = < 0.001）显著相关。吉非替尼在经治的晚期NSCLC患者中显示出相关的临床活性和良好的毒性特征。毒性的出现与良好的反应相关。此外，从不吸烟史似乎预示着吉非替尼有更高的疗效。
