Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck
Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1200/jco.2003.10.051
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发表时间：
2003-05-15
影响因子：
45.3
通讯作者：
Vokes, EE
中科院分区：
文献类型：
--
作者：
Cohen, EEW;Rosen, F;Vokes, EE
目的：表皮生长因子受体（EGFR）是头颈部鳞状细胞癌（SCCHN）发生发展的介导因子。ZD 1839是一种口服活性、选择性EGFR酪氨酸激酶抑制剂。本II期研究旨在探讨ZD 1839在SCCHN.Patients和Methods中的活性、毒性和药效学：通过芝加哥大学II期联盟招募复发性或转移性SCCHN患者。允许患者接受不超过一种复发性或转移性疾病的既往治疗，并接受ZD 1839 500 mg/d单药治疗。获得患者肿瘤活检组织，并对EGFR、细胞外信号调节激酶1（ERK 1）和磷酸化ERK 1（p-ERK）进行化学染色。研究终点包括反应率，进展时间，中位生存期，和抑制p-ERK.Results：52例患者入组（40名男性和12名女性），中位年龄为59岁（范围，34至84岁）。14例患者通过饲管接受ZD 1839。一半队列接受ZD 1839作为第二精细治疗。47例患者可评估缓解，观察到的缓解率为10.6%，疾病控制率为53%。中位进展时间和生存期分别为3.4和8.1个月。唯一遇到的3级毒性是3名患者的腹泻。发现体能状态和皮肤毒性的发展是反应、进展和生存的强预测因子。10个活检样本进行了评估，并显示EGFR或p-ERK表达与ZD 1839 therapeutic.Conclusion：ZD 1839具有单药活性，在难治性SCCHN耐受性良好。与其他报告相比，皮肤毒性的发生是缓解和结局改善的统计学显著预测因素。(C)2003年，美国临床肿瘤学会。
Purpose: The epidermal growth factor receptor (EGFR) is a mediator of squamous cell carcinoma of the head and neck (SCCHN) development. ZD1839 is an orally active, selective EGFR tyrosine kinase inhibitor. This phase II study sought to explore the activity, toxicity, and pharmocodynamics of ZD1839 in SCCHN.Patients and Methods: Patients with recurrent or metastatic SCCHN were enrolled through the University of Chicago Phase II Consortium. Patients were allowed no more than one prior therapy for recurrent or metastatic disease and were treated with single-agent ZD1839 500 mg/d. Patient tumor biopsies were obtained and stained immunohistochemically for EGFR, extracellular signal-regulated kinase 1 (ERK1), and phosphorylated ERK1 (p-ERK). Study end points included response rate, time to progression, median survival, and inhibition of p-ERK.Results: Fifty-two patients were enrolled (40 male and 12 female) with a median age of 59 years (range, 34 to 84 years). Fourteen patients received ZD1839 through a feeding tube. Half the cohort received ZD1839 as second-fine therapy. Forty-seven patients were assessable for response, with an observed response rate of 10.6% and a disease control rate of 53%. Median time to progression and survival were 3.4 and 8.1 months, respectively. The only grade 3 toxicity encountered was diarrhea in three patients. Performance status and development of skin toxicity were found to be strong predictors of response, progression, and survival. Ten biopsy samples were assessable and revealed no significant change in EGFR or p-ERK expression with ZD1839 therapy.Conclusion: ZD1839 has single-agent activity and is well tolerated in refractory SCCHN. In contrast to other reports, development of skin toxicity was a statistically significant predictor of response and improved outcome. (C) 2003 by American Society of Clinical Oncology.