Herbst Roy S, Hong Waun Ki
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Semin Oncol. 2002 Oct;29(5 Suppl 14):18-30. doi: 10.1053/sonc.2002.35644.
Squamous cell carcinoma of the head and neck remains a clinical challenge because of the high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumors, including squamous cell carcinoma of the head and neck, is well understood; increased expression is associated with enhanced tumor invasiveness, resistance to chemotherapy, and a lower patient survival rate. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including the anti-EGFR monoclonal antibody IMC-C225, which competitively binds to the extracellular receptor site and prevents binding by the natural EGFR ligands EGF and transforming growth factor-alpha. Preclinical studies to evaluate IMC-225 in human cancer cell lines in vitro and human tumor xenografts in vivo have shown its potent antitumor activity. Clinical efficacy of IMC-C225 appears to involve multiple mechanisms, including inhibition of cell cycle progression, induction of apoptosis, inhibition of angiogenesis, inhibition of metastasis, and enhancement of the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation showed promising response rates in patients with recurrent or refractory squamous cell carcinoma of the head and neck. Phase II and III trials to examine the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m(2) loading dose, followed by weekly infusions at 250 mg/m(2).
由于局部区域疾病复发率高，头颈部鳞状细胞癌仍然是一项临床挑战。表皮生长因子受体（EGFR）在包括头颈部鳞状细胞癌在内的许多实体瘤的发生和发展中的重要性已得到充分认识；表达增加与肿瘤侵袭性增强、化疗耐药性以及患者生存率降低相关。已经开发了几种方法来实现EGFR阻断作为一种抗癌治疗策略，包括抗EGFR单克隆抗体IMC-C225，它竞争性地结合细胞外受体位点并阻止天然EGFR配体表皮生长因子（EGF）和转化生长因子-α的结合。在体外人癌细胞系和体内人肿瘤异种移植模型中评估IMC-225的临床前研究已显示出其强大的抗肿瘤活性。IMC-C225的临床疗效似乎涉及多种机制，包括抑制细胞周期进程、诱导凋亡、抑制血管生成、抑制转移以及增强对化疗和放疗的反应。IMC-C225联合化疗或放疗的I期研究显示，对头颈部复发或难治性鳞状细胞癌患者有令人鼓舞的缓解率。目前正在进行II期和III期试验以检验这些联合治疗的疗效和安全性。迄今为止，IMC-C225耐受性良好，皮疹和过敏反应是报告的最主要临床不良事件。IMC-C225显示出剂量依赖性消除特征，半衰期约为7天。目前的给药建议包括400mg/m²的负荷剂量，随后每周输注250mg/m²。
