National Institute of Oncology and Radiobiology, Havana, Cuba.
Cancer Biol Ther. 2010 Mar 1;9(5):343-9. doi: 10.4161/cbt.9.5.10981. Epub 2010 Mar 20.
The prognosis of patients with advanced head and neck cancer remain dismal. For this tumor type, elevated levels of EGFR are associated with a shorter disease free survival and time to treatment failure, reflecting a more aggressive phenotype. Nimotuzumab is a humanized monoclonal antibody that recognizes domain III of the extracellular region of the EGFR, within an area that overlaps with both the surface patch recognized by cetuximab and the binding site for EGF. In order to assess the efficacy of nimotuzumab in combination with radiotherapy, a controlled, double blind, randomized clinical trial was conducted in 106 advanced squamous cell carcinoma of the head and neck patients, mostly, unfit for chemoradiotherapy. Control patients received a placebo and radiotherapy. Treatment was safe and the most frequent adverse events consisted on grade I or II asthenia, fever, headache and chills. No skin rash was detected. A significant complete response rate improvement was found in the group of patients treated with nimotuzumab as compared to the placebo. In the intent to treat analysis, a trend towards survival benefit for nimotuzumab treated subjects was found. The survival benefit became significant when applying the Harrington-Fleming test, a weighted log-rank that underscores the detection of differences deferred on time. In addition, a preliminary biomarker investigation showed a significant survival improvement for nimotuzumab treated patients as compared to controls for subjects with EGFR positive tumors. All patients showed a quality of life improvement and a reduction of the general and specific symptoms of the disease.
晚期头颈部癌症患者的预后仍然不容乐观。对于这种肿瘤类型，EGFR 水平升高与无疾病生存时间和治疗失败时间缩短相关，反映了更具侵袭性的表型。尼妥珠单抗是一种人源化单克隆抗体，可识别 EGFR 细胞外区域的 III 结构域，该区域与西妥昔单抗识别的表面斑块和 EGF 结合部位重叠。为了评估尼妥珠单抗联合放疗的疗效，在 106 例不适合放化疗的晚期头颈部鳞状细胞癌患者中进行了一项对照、双盲、随机临床试验。对照组患者接受安慰剂和放疗。治疗安全，最常见的不良反应为 I 级或 II 级乏力、发热、头痛和寒战。未发现皮疹。与安慰剂组相比，尼妥珠单抗治疗组患者的完全缓解率显著提高。在意向治疗分析中，尼妥珠单抗治疗组患者的生存获益呈趋势。当应用强调检测时间延迟差异的哈林顿-弗莱明检验（一种加权对数秩检验）时，生存获益变得显著。此外，初步的生物标志物研究表明，与对照组相比，EGFR 阳性肿瘤患者接受尼妥珠单抗治疗的患者生存时间显著改善。所有患者的生活质量均得到改善，疾病的一般和特定症状均得到减轻。
