Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023
Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023
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DOI：
10.1200/jco.2007.14.4824
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发表时间：
2008-05-20
影响因子：
45.3
通讯作者：
Gandara, David R.
中科院分区：
文献类型：
--
作者：
Kelly, Karen;Chansky, Kari;Gandara, David R.
目的吉非替尼的早期临床研究显示出对晚期非小细胞肺癌 (NSCLC) 患者的良好疗效和轻微毒性。因此，吉非替尼是在 III 期疾病的维持环境中进行评估的理想药物。 患者和方法 未经治疗的 III 期 NSCLC 患者、体能评分为 0 到 1 且器官功能充足的患者符合资格。所有患者在第 1 天和第 8 天接受顺铂 50 mg/m(2)，加第 1 天至第 5 天接受依托泊苷 50 mg/m(2)，每 28 天一次，共两个周期，同时进行胸部放射（每天 1.8 至 2 Gy 剂量；总剂量，61 Gy），随后接受三个周期的多西紫杉醇 75 mg/m(2)。疾病未进展的患者被随机分配至吉非替尼 250 mg/d 或安慰剂组，直至疾病进展、出现无法耐受的毒性或 5 年后结束。计划的样本量为 672 名患者，功效为 0.89，检测到预期中位生存时间比 21 个月增加了 33%（单边 P = 0.025，对数秩检验）。随机分配按分期、组织学以及可测量疾病与不可测量疾病进行分层。结果 招募于 2001 年 7 月开始。2005 年 4 月进行的计划外中期分析拒绝了 243 名随机分配患者的生存率提高（P = 0.0015 水平）的替代假设。研究结束，并报告了初步结果。现在，中位随访时间为 27 个月，吉非替尼组的中位生存时间为 23 个月 (n = 118)，安慰剂组为 35 个月 (n = 125；双侧 P = 0.013)。吉非替尼组的中毒性死亡率为 2%，而安慰剂组为 0%。 结论 在这个未经选择的人群中，吉非替尼没有改善生存率。生存率下降是肿瘤进展的结果，而不是吉非替尼毒性的结果。
PurposeEarly clinical studies with gefitinib showed promising efficacy and mild toxicity in patients with advanced non-small-cell lung cancer (NSCLC). Thus, gefitinib was an ideal agent to evaluate in a maintenance setting in stage III disease.Patients and MethodsUntreated patients with stage III NSCLC, a performance score of 0 to 1, and adequate organ function were eligible. All patients received cisplatin 50 mg/m(2) on days 1 and 8 plus etoposide 50 mg/m(2) on days 1 to 5, every 28 days for two cycles with concurrent thoracic radiation (1.8- to 2-Gy fractions per day; total dose, 61 Gy) followed by three cycles of docetaxel 75 mg/m(2). Patients whose disease did not progress were randomly assigned to gefitinib 250 mg/d or placebo until disease progression, intolerable toxicity, or the end of 5 years. The planned sample size was 672 patients to confer power of 0.89 to detect a 33% increase over the expected median survival time of 21 months (one-sided P = .025, log-rank test). Random assignment was stratified by stage, histology, and measurable versus nonmeasurable disease.ResultsEnrollment began in July 2001. An unplanned interim analysis conducted in April 2005 rejected the alternative hypothesis of improved survival at the P = .0015 level for 243 randomly assigned patients. The study closed, and preliminary results were reported. Now, with a median follow-up time of 27 months, median survival time was 23 months for gefitinib (n = 118) and 35 months for placebo (n = 125; two-sided P = .013). The toxic death rate was 2% with gefitinib compared with 0% for placebo.ConclusionIn this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.