Cohen Ezra E W
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
J Clin Oncol. 2006 Jun 10;24(17):2659-65. doi: 10.1200/JCO.2005.05.4577.
The development of epidermal growth factor receptor (EGFR) inhibitors was greeted with tremendous enthusiasm in the therapy of squamous cell carcinoma of the head and neck (SCCHN) based on the nearly universal expression of this protein, the negative prognostic associations with expression, and robust preclinical data. Clinical trials to date have demonstrated modest activity of these drugs as single agents with reproducible major response rates of 5% to 15% in SCCHN depending on agent, dose, and schedule. The biology of responsiveness to these agents remains unclear, although an association of development of cutaneous toxicity with positive outcome has been reported repeatedly. Nevertheless, molecular markers of response or resistance have yet to be fully delineated. In the near future, phase III clinical trials will elucidate the role of these agents in second-line recurrent and/or metastatic (R/M) disease, the combination of EGFR inhibitors with other therapeutic strategies will be broadly advanced, and a set of molecular predictors of benefit will begin to emerge. This article will review the progress in utilization of EGFR inhibitors in R/M SCCHN.
基于表皮生长因子受体(EGFR)在头颈部鳞状细胞癌(SCCHN)中几乎普遍表达、其表达与不良预后相关以及有力的临床前数据,EGFR抑制剂的研发在头颈部鳞状细胞癌治疗中受到了极大的热情关注。迄今为止的临床试验表明,这些药物作为单药使用时活性一般,在头颈部鳞状细胞癌中,根据药物、剂量和给药方案的不同,可重复的主要缓解率为5%至15%。尽管反复报道皮肤毒性的发生与良好预后相关,但对这些药物反应的生物学机制仍不清楚。然而,反应或耐药的分子标志物尚未完全明确。在不久的将来,III期临床试验将阐明这些药物在二线复发和/或转移性(R/M)疾病中的作用,EGFR抑制剂与其他治疗策略的联合应用将得到广泛推进,并且一系列获益的分子预测指标将开始出现。本文将综述EGFR抑制剂在R/M SCCHN治疗中的应用进展。