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Treatment of Recurrent Metastatic Head and Neck Cancer: Focus on Cetuximab

机译:复发性转移性头颈癌的治疗:集中在西妥昔单抗上

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摘要

EGFR belongs to the ErbB family of receptor tyrosine kinases and is associated with worse prognosis in head and neck squamous cell carcinoma (HNSCC). Cetuximab is a monoclonal antibody to the extracellular domain of EGFR and inhibits its downstream actions via multiple mechanisms. Besides its proven efficacy in locally advanced and incurable HNSCC, cetuximab has the distinct advantage of having a relatively tolerable side effect profile and not potentiating radiation toxicity. Though therapies for advanced HNSCC are evolving, locoregional recurrence and/or distant metastases occur in a large percentage of patients. Though some patients can be salvaged with surgery or radiation therapy, the majority are incurable, and are treated palliatively with systemic therapy. In the setting of first line therapy for recurrent/metastatic HNSCC, the EXTREME trial provided level 1 evidence that cetuximab improves overall survival when combined with cisplatinum and 5 FU. Following progression on first line chemotherapy, several phase II trials suggest that cetuximab monotherapy is a reasonable choice in this setting. Future studies should concentrate on clinical and molecular markers that may allow more personalized approaches to treating HNSCC, and combining EGFR inhibitors with other agents in a synergistic approach.
机译:EGFR属于受体酪氨酸激酶的ErbB家族,与头颈部鳞状细胞癌(HNSCC)的预后较差有关。西妥昔单抗是针对EGFR细胞外结构域的单克隆抗体,可通过多种机制抑制其下游作用。西妥昔单抗除了在局部晚期和无法治愈的HNSCC中被证明具有疗效外,还具有明显的优势,即具有相对可耐受的副作用,并且不增强放射毒性。尽管晚期HNSCC的治疗方法正在不断发展,但仍有很大一部分患者发生局部复发和/或远处转移。尽管可以通过手术或放射疗法挽救一些患者,但大多数患者是无法治愈的,可以通过全身疗法进行姑息治疗。在复发/转移性HNSCC一线治疗的背景下,EXTREME试验提供了1级证据,证明西妥昔单抗与顺铂和5 FU联合使用可提高总体生存率。随着一线化疗的进展,一些II期临床试验表明西妥昔单抗单药治疗是这种情况下的合理选择。未来的研究应集中在临床和分子标志物上,这些标志物可能允许采用更具个性化的方法治疗HNSCC,并以协同方式将EGFR抑制剂与其他药物结合使用。

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