CHEMORADIOTHERAPY PLUS C225 (CETUXIMAB) FOR ADVANCED SQUAMOUS CELL CARCINOMA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在美国，每年大约有43,000例头颈部鳞状细胞癌被诊断出来。大约三分之二的患者出现晚期疾病（III期或IV期）。近年来，通过改进强化放疗计划和/或使用联合放化疗方法，成功的非手术治疗策略取得了相当大的进展。尽管如此，对于许多晚期但可切除的头颈部鳞状细胞癌患者，手术切除后术后放射治疗仍然是一种常见的治疗方法。尽管积极的手术和辅助放疗，许多患者仍然屈服于局部疾病复发。远处转移（最常见于肺部）也可发生在晚期头颈癌患者中，并且在最终治疗后局部区域疾病复发的患者中，这种事件的发生频率增加。已发表的报告显示，在接受手术和术后放射治疗的晚期头颈癌患者中，约有四分之一至三分之一的患者会出现局部区域疾病复发。减少复发率的努力主要集中在术后联合放化疗上。主要目的：采用随机分配II期设计，评估在高危术后头颈部患者中使用EGFR抑制剂C225联合放化疗的两种治疗方案。该试验旨在确定两种方案是否有足够的希望在随后的III期研究中继续进行。这一决定将主要基于在已完成的组间试验RTOG 9501中接受放化疗的类似患者的无病生存期相对于RTOG数据库是否有改善。次要目的：1)确定晚期头颈癌手术切除后各治疗方案能否安全、成功地交付。2)评估各方案治疗患者的局部控制率和总生存率。3)检测EGFR（总和磷酸化）、pMAPK、pAKT、Stat-3、Ki-67、COX-2和cyclin B1表达与最终治疗结果的相关性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are approximately 43,000 cases of head and neck squamous cell carcinoma diagnosed annually in the United States. Approximately two thirds of these patients present with advanced disease (Stage III or IV). Successful nonoperative treatment strategies have advanced considerably over recent years through the refinement of intensified radiation fractionation schedules and/or the use of combination chemoradiation approaches. Nonetheless, for many patients with advanced but resectable squamous cell carcinoma of the head and neck, surgical resection followed by postoperative radiation therapy remains a common treatment approach. Despite aggressive surgery and adjuvant radiation, many patients still succumb to locoregional disease recurrence. Distant metastases (most commonly to the lungs) can also occur in advanced head and neck cancer patients, and the frequency of this event is increased in patients who suffer locoregional disease recurrence following definitive therapy. Published reports suggest that approximately one quarter to one third of advanced head and neck cancer patients treated with surgery and postoperative radiation therapy experience locoregional disease recurrence. Efforts to diminish these recurrence rates have focused primarily on combined chemoradiation in the postoperative setting. Primary Objective: To evaluate, using a random assignment phase II design, two treatment regimens that utilize the EGFR inhibitor C225 in combination with chemoradiation in high-risk postoperative head and neck patients. This trial is designed to determine if either regimen is promising enough to be pursued in a pursued in a subsequent phase III study. This decision will be primarily based on whether there is improvement in disease-free survival relative to the RTOG database of similar patients treated with chemoradiation in the completed intergroup trial RTOG 9501. Secondary Objective: 1) To determine whether each of the treatment regimens can be delivered safely and successfully following surgical resection for advanced head and neck cancer. 2) To estimate the locoregional control and overall survival rates for patients treated with the each regimen. 3) To examine the correlation between EGFR (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, COX-2, and cyclin B1 expression with the ultimate treatment outcome.