Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck

被引:471
作者
Cohen, EEW
Rosen, F
Stadler, WM
Recant, W
Stenson, K
Huo, DZ
Vokes, EE
机构
[1] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA
[2] Univ Chicago, Sect Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA
[3] Univ Chicago, Urol Sect, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[5] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[6] Univ Chicago, Dept Surg, Chicago, IL 60637 USA
[7] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA
[8] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA
[9] Univ Illinois, Dept Med, Hematol Oncol Sect, Chicago, IL USA
关键词
D O I
10.1200/JCO.2003.10.051
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:1980 / 1987
页数:8
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