Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT1
Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase III trial-INTACT1
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DOI：
10.1200/jco.2004.08.001
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发表时间：
2004-03-01
影响因子：
45.3
通讯作者：
Johnson, DH
中科院分区：
文献类型：
--
作者：
Giaccone, G;Herbst, RS;Johnson, DH
目的本研究的目的是确定在标准一线吉西他滨和顺铂治疗中加入表皮生长因子受体酪氨酸激酶抑制剂吉非替尼（易瑞沙，ZD 1839;阿斯利康，威尔明顿，DE）是否比单独吉西他滨和顺铂治疗晚期或转移性非小细胞肺癌（NSCLC）患者提供临床获益。吉非替尼已经证明了令人鼓舞的疗效在晚期非小细胞肺癌在11期临床试验中的预处理患者，和吉非替尼与吉西他滨和顺铂相结合的I期试验显示出良好的tolerancel.Patients和方法这是一个III期随机，双盲，安慰剂对照，化疗初治患者不可切除的III期或IV期非小细胞肺癌的多中心试验。所有患者均接受最多6个周期的化疗（顺铂80 mg/m2，第1天;吉西他滨1,250 mg/m2，第1天和第8天，3周为1个周期）加吉非替尼500 mg/d、吉非替尼250 mg/d或安慰剂。每日服用吉非替尼或安慰剂，直至疾病进展。终点包括总生存期（主要），进展时间，反应率和安全性evaluation.Results共1,093例患者参加。治疗组之间的疗效终点没有差异：吉非替尼500 mg/d、吉非替尼250 mg/d和安慰剂组的中位生存时间分别为9.9、9.9和10.9个月（全局有序对数秩[GOLrank] P =.4560），中位至进展时间分别为5.5、5.8和6.0个月（GOLrank; P =.7633），应答率分别为49.7%、50.3%和44.8%。未观察到显著的非预期不良事件。(C)结论吉非替尼联合吉西他滨和顺铂治疗初治晚期NSCLC患者的疗效并不优于单用吉西他滨和顺铂。其原因尚不清楚，需要进一步的临床前试验。
Purpose The purpose of this study was to determine whether the addition of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE) to standard first-line gemcitabine and cisplatin provides clinical benefit over gemcitabine and cisplatin alone in patients with advanced or metastatic non-small-cell lung cancer (NSCLC). Gefitinib has demonstrated encouraging efficacy in advanced NSCLC in phase 11 trials in pretreated patients, and a phase I trial of gefitinib in combination with gemcitabine and cisplatin showed favorable tolerability.Patients and Methods This was a phase III randomized, double-blind, placebo-controlled, multicenter trial in chemotherapy-naive patients with unresectable stage III or IV NSCLC. All patients received up to six cycles of chemotherapy (cisplatin 80 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 of the 3-week cycle) plus either gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. Daily gefitinib or placebo was continued until disease progression. End points included overall survival (primary), time to progression, response rates, and safety evaluation.Results A total of 1,093 patients were enrolled. There was no difference in efficacy end points between the treatment groups: for the gefitinib 500 mg/d, gefitinib 250 mg/d, and placebo groups, respectively, median survival times were 9.9, 9.9, and 10.9 months (global ordered log-rank [GOLrank] P =.4560), median times to progression were 5.5, 5.8, and 6.0 months (GOLrank; P =.7633), and response rates were 49.7%, 50.3%, and 44.8%. No significant unexpected adverse events were seen.(C) 2004 by American Society of Clinical Oncology.Conclusion Gefitinib in combination with gemcitabine and cisplatin in chemotherapy-naive patients with advanced NSCLC did not have improved efficacy over gemcitabine and cisplatin alone. The reasons for this remain obscure and require further preclinical testing.