Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Phase II trial of gefitinib 250 mg daily in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1158/1078-0432.ccr-05-1247
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发表时间：
2005-12-01
影响因子：
11.5
通讯作者：
Vokes, EE
中科院分区：
文献类型：
--
作者：
Cohen, EEW;Kane, MA;Vokes, EE
目的：尽管肺癌的推荐剂量为250 mg，但接受吉非替尼每日500 mg治疗的复发性和/或转移性头颈部鳞状细胞癌（SCCHN）患者的客观缓解率为11%。本研究评价了250毫克每日吉非替尼在复发和/或转移性SCCHN.Experimental设计：II期临床试验的疗效和毒性，客观反应率为主要终点。结果：70例患者中，部分缓解1例（1.4%），部分缓解1例（1.4%），部分缓解1例（1.4%）。中位无进展生存期和总生存期分别为1.8和5.5个月。在治疗的第一周，生活质量评分短暂改善，然后恢复到基线。中位血管内皮生长因子和转化生长因子-α水平高于正常范围，但不能预测结局。4例患者发生3级药物相关不良事件。在64%的受试者中观察到任何级别的皮疹。疾病控制（部分反应+稳定的疾病），无进展生存期，总生存期和皮肤毒性等级之间的相关性进行了观察（P = 0.001，0.001，和0.008分别）。结论：吉非替尼单药治疗复发性和/或转移性SCCHN在250毫克似乎有较低的活性比以前观察到的500毫克每天。该药物在SCCHN中可能存在剂量-反应关系，吉非替尼的皮肤毒性等级是更好结局的临床预测因子。
Purpose: An objective response rate of 11% was reported in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) treated with 500 mg daily gefitinib although the recommended dose in lung cancer is 250 mg. This study evaluated the efficacy and toxicity of 250 mg daily gefitinib in patients with recurrent and/or metastatic SCCHN.Experimental Design: Phase II trial with objective response rate as the primary end point. Measurements of quality of life and levels of Serum vascular endothelial growth factor and transforming growth factor-alpha were assessed before and during therapy.Results: In 70 patients, 1 (1.4%) partial response was observed. Median progression-free survival and overall survival were 1.8 and 5.5 months, respectively. Quality of life scores improved transiently during the first weeks of therapy before returning to baseline. Median vascular endothelial growth factor and transforming growth factor-alpha levels were above the normal range but were not predictive of outcome. Four patients experienced grade 3 drug-related adverse events. Rash of any grade was observed in 64% of subjects. Correlation between disease control (partial response + stable disease), progression-free survival, and overall survival and grade of cutaneous toxicity was observed (P = 0.001, 0.001, and 0.008 respectively).Conclusions: Gefitinib monotherapy at 250 mg in recurrent and/or metastatic SCCHN seems to have less activity than was previously observed for 500 mg daily. A dose-response relationship may exist for this agent in SCCHN and grade of cutaneous toxicity attributable to gefitinib is a clinical predictor of better outcome.