尼妥珠单抗联合放疗加同期替莫唑胺治疗高分级胶质瘤的初步研究

Primary study of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy treatment for high-grade glioma

背景与目的:尼妥珠单抗(nimotuzumab)是抗人表皮生长因子受体(epithelial growth factor receptor,EGFR)人源化单克隆抗体,能够抑制肿瘤细胞增殖并增加放化疗敏感性。本研究运用前瞻性方法对尼妥珠单抗联合放疗加同期替莫唑胺(temozolomide,TMZ)治疗高分级的脑胶质瘤(high-grade glioma,HGG)患者的不良反应和近期疗效进行初步观察。方法:2008年7月—2009年6月期间共17例HGG患者入组,均采用TMZ同期放化疗加TMZ辅助化疗,其中12例新诊断为HGG的患者放疗总剂量为60Gy/30次,3例复发HGG患者为50Gy/25次,2例脑干复发HGG患者为40Gy/20次;放疗期间每天口服TMZ50mg/m2,放疗结束后4周循环口服TMZ;放疗期间每周静脉滴注尼妥珠单抗注射液。记录治疗反应,计算6个月无疾病进展生存率和总生存率。结果:本组病例急性不良反应多为Ⅰ～Ⅱ级,没有Ⅲ级以上不良反应,有1例因发生Ⅱ级湿疹性皮炎,从而中断尼妥珠单抗治疗。16例作近期疗效评价,其中PR4例,SD10例,PD2例。6个月无进展生存率和总生存率分别为72.1%和86.3%。其中3例发生肿瘤假性进展。结论:本研究初步显示尼妥珠单抗联合放疗加同期替莫唑胺治疗HGG不良反应较小,患者可以耐受,近期疗效较好,远期疗效尚需进一步观察。

Background and purpose： Nimotuzumab is a humanized monoclonal antibody that inhibits tumor cells and enhances chemoradiosensitivity. This study evaluated the side-effect and outcome of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy treatment for high-grade glioma prospectively. Methods： From Jul. 2008 to Jun. 2009, 17 cases of HGG were included in this study. All patients received radiotherapy （60 Gy/28 fx for 13 cases with newly diagnosed HGG, 50 Gy/25 fx for 3 cases with recurrent HGG, and 40 Gy/20 fx for 2 cases with recurrent brainstem glioma） and concomitant temozolomide chemotherapy （50 mg/m2 daily during RT until completion of RT） followed by TMZ adjuvant chemotherapy. Nimotuzumab was used by weekly injection during RT. The treatment reactions were recorded. Six month progression-free survival rate and overall survival rate were calculated. Results： Grade Ⅰ - Ⅱ of acute treatment toxicity was found, toxicity of more than grade 111 was not observed. Eczematoid dermatitis was diagnosed after the use of nimotuzumab in one case, who refused further nimotuzumab treatment. All of the 16 cases for evaluation, there were 4 cases with PR, 10 cases with SD, 2 cases with PD. The 6-month progression-free survival rate and overall survival rate were 72.1% and 86.3%, respectively. 3 cases with pseudoprogression were found. Conclusion： Primary study demonstrated that the use of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy is effective for high-grade glioma, and the side-effect was mild and acceptable. Long-term outcome should be investigated with caution.