Ahmed Syed M, Cohen Ezra E W
Section of Hematology/Oncology, Department of Medicine, The University of Chicago Medical Center, The Pritzker School of Medicine, Chicago, IL 60637, USA.
Curr Cancer Drug Targets. 2007 Nov;7(7):666-73. doi: 10.2174/156800907782418293.
Approximately 475,000 cases of squamous cell carcinoma (SCCHN) of the head and neck occur worldwide. Whereas significant advances have been made in the treatment of early and locally advanced disease, the prognosis for recurrent and metastatic (R/M) disease remains poor. Compounds with demonstrated activity include cisplatin and carboplatin, antimicrotubular compounds such as taxanes and vinorelbine, and fluoropyrimidines. In refractory and metastatic disease, regimens combining platinum agents with taxanes or fluorouracil based agents produce a 30% response rate and a median overall survival of six to eight months. Newer three agent chemotherapy regimens have produced response rates in the range of 40-50%, without significant improvements in overall survival noted. Recently, a new class of medications targeting signal transduction pathways has come into focus in the treatment of various malignancies. In SCCHN, given the high prevalence of expression of the epidermal growth factor receptor (EGFR) and its role in promoting cellular growth and proliferation, molecules targeting the receptor's intracellular kinase domain are a logical strategy. The agents gefitinib and erlotinib have yielded response rates in the 5-15% range when used as single agents. In addition, newer agents with broad activity against the EGFR and other related erbB receptor family members are being developed in clinical trials. Strategies to enhance the activity of EGFR tyrosine kinase inhibitors (TKIs) in treating SCCHN are being investigated, as well as strategies to select individuals with tumors more likely to respond to these drugs. This article reviews the advances that have made in treating refractory and metastatic disease, with particular focus on the challenges that are faced in successfully translating EGFR inhibition as a paradigm of tumor treatment in SCCHN.
全球范围内，每年约有47.5万例头颈部鳞状细胞癌（SCCHN）病例。尽管早期和局部晚期疾病的治疗已取得显著进展，但复发和转移性（R/M）疾病的预后仍然很差。已证实具有活性的化合物包括顺铂和卡铂、抗微管化合物如紫杉烷和长春瑞滨，以及氟嘧啶。在难治性和转移性疾病中，铂类药物与紫杉烷或氟尿嘧啶类药物联合使用的方案产生了30%的缓解率，中位总生存期为6至8个月。新的三联化疗方案的缓解率在40%-50%之间，但总体生存期没有显著改善。最近，一类针对信号转导通路的新型药物在各种恶性肿瘤的治疗中受到关注。在SCCHN中，鉴于表皮生长因子受体（EGFR）表达率高及其在促进细胞生长和增殖中的作用，靶向该受体细胞内激酶结构域的分子是一种合理的策略。吉非替尼和厄洛替尼作为单药使用时，缓解率在5%-15%之间。此外，在临床试验中正在开发对EGFR和其他相关erbB受体家族成员具有广泛活性的新型药物。正在研究增强EGFR酪氨酸激酶抑制剂（TKIs）治疗SCCHN活性的策略，以及选择更可能对这些药物有反应的肿瘤患者的策略。本文综述了难治性和转移性疾病治疗方面的进展，特别关注将EGFR抑制成功转化为SCCHN肿瘤治疗范例所面临的挑战。
