Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer
Phase II, open-label, randomized study (SIGN) of single-agent gefitinib (IRESSA) or docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer
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DOI：
10.1097/01.cad.0000203381.99490.ab
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发表时间：
2006-04-01
影响因子：
2.3
通讯作者：
Pemberton, Kristine
中科院分区：
文献类型：
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作者：
Cufer, Tania;Vrdoljak, Eduard;Pemberton, Kristine
我们的目的是评估吉非替尼（易瑞沙），一种表皮生长因子受体酪氨酸激酶抑制剂，与多西他赛作为二线单药治疗晚期非小细胞肺癌（NSCLC）。SIGN（吉非替尼在NSCLC中的二线适应症;代码1839 IL/0503）是一项多中心、随机、平行组、开放标签、11期试验，研究口服吉非替尼（250 mg/天）或静脉注射多西他赛（75 mg/m2，每3周一次）治疗既往接受过一种化疗方案的晚期NSCLC患者。主要目的是评估症状改善（使用FACT-L肺癌子量表）。次要目的包括生活质量（FACT-L总分）、缓解率（使用RECIST）、总生存期和安全性。该试验招募了141例患者（68例接受吉非替尼治疗，73例接受多西他赛治疗），接受治疗的中位持续时间为3.0（吉非替尼）和2.8（多西他赛）个月。吉非替尼和多西他赛的疗效相似，症状改善率分别为36.8%和26.0%，生活质量改善率分别为33.8%和26.0%，客观缓解率分别为13.2%和13.7%，中位总生存期分别为7.5和7.1个月。与多西他赛相比，吉非替尼组观察到的药物相关不良事件较少（所有等级：51.5 vs 78.9%;常见毒性标准3/4级：8.8 vs 25.4%）。吉非替尼组没有因药物相关不良事件而退出或死亡，而多西他赛组有3名患者退出，3名患者因可能与药物相关的不良事件而死亡。我们得出结论，吉非替尼的疗效与多西他赛相似，但在晚期NSCLC的二线治疗中具有更有利的耐受性。这些结果支持进一步研究吉非替尼在这种疾病的设置。
Our objective was to evaluate gefitinib (IRESSA), an epidermal growth factor receptor tyrosine kinase inhibitor, versus docetaxel as second-line monotherapy for advanced non-small-cell lung cancer (NSCLC). SIGN (Second-line Indication of Gefitinib in NSCLC; code 1839IL/0503) was a multicenter, randomized, parallel-group, open-label, phase 11 trial that investigated oral gefitinib (250 mg/day) or i.v. docetaxel (75 mg/m(2) every 3 weeks) in patients with advanced NSCLC who had previously received one chemotherapy regimen. The primary objective was assessment of symptom improvement (using the FACT-L Lung Cancer Subscale). Secondary objectives included quality of life (FACT-L total score), response rate (using RECIST), overall survival and safety. This trial recruited 141 patients (68 to gefitinib and 73 to docetaxel) who received treatment for a median duration of 3.0 (gefitinib) and 2.8 (docetaxel) months. Similar efficacy was observed with gefitinib and docetaxel, 36.8 and 26.0% symptom improvement rates, 33.8 and 26.0% quality-of-life improvement rates, 13.2 and 13.7% objective response rates, and 7.5 and 7.1 months median overall survival, respectively. Fewer drug-related adverse events were observed with gefitinib compared with docetaxel (all grades: 51.5 versus 78.9%; Common Toxicity Criteria grade 3/4: 8.8 versus 25.4%). There were no withdrawals or deaths due to drug-related adverse events with gefitinib, while three patients withdrew and three died due to adverse events in the docetaxel group that were possibly drug related. We conclude efficacy with gefitinib was similar to docetaxel, but with a more favorable tolerability profile, in the second-line treatment of advanced NSCLC. These results support further investigation of gefitinib in this disease setting.