CAJ | 학술논문

目的：恶性胶质瘤的预后较差，急需探索新的治疗策略以提高疗效。尼妥珠单抗是一种人源化抗表皮生长因子受体的单克隆抗体，能够抑制肿瘤细胞增殖，在一些恶性胶质瘤的Ⅰ/Ⅱ期临床研究中显示出了良好的耐受性及有效性。为此进行Ⅰ期临床试验，观察尼妥珠单抗联合术后同步放化疗治疗恶性胶质瘤的药物不良反应，耐受剂量及临床可行性。方法：选取经病理确诊的Ⅲ～Ⅳ级脑胶质瘤术后患者为研究对象，采用术后替莫唑胺同步放化疗的标准治疗方案加尼妥珠单抗靶向治疗。尼妥珠单抗分100、200、400 mg/周3个剂量级，每剂量组3～6例，从低剂量组开始用药，如3例均未出现3级以上不良反应则进入下一剂量组。尼妥珠单抗采用静脉滴注，放疗期间1次/周，共6次。结果：共有9例恶性胶质瘤入组，其中Ⅲ级胶质瘤7例，Ⅳ级2例。治疗过程中出现的不良反应均为1～2级，骨髓抑制为最常见的不良反应。临床治疗剂量达到400 mg/周时并未出现3级以上不良反应，可良好耐受。3个月后评价近期疗效，5例病情稳定，4例出现进展。结论：本研究显示尼妥珠单抗联合术后同步放化疗对于治疗华人恶性胶质瘤的不良反应轻微，可良好耐受。
목적：악성효질류적예후교차，급수탐색신적치료책략이제고료효。니타주단항시일충인원화항표피생장인자수체적단극륭항체，능구억제종류세포증식，재일사악성효질류적Ⅰ/Ⅱ기림상연구중현시출료량호적내수성급유효성。위차진행Ⅰ기림상시험，관찰니타주단항연합술후동보방화료치료악성효질류적약물불량반응，내수제량급림상가행성。방법：선취경병리학진적Ⅲ～Ⅳ급뇌효질류술후환자위연구대상，채용술후체막서알동보방화료적표준치료방안가니타주단항파향치료。니타주단항분100、200、400 mg/주3개제량급，매제량조3～6례，종저제량조개시용약，여3례균미출현3급이상불량반응칙진입하일제량조。니타주단항채용정맥적주，방료기간1차/주，공6차。결과：공유9례악성효질류입조，기중Ⅲ급효질류7례，Ⅳ급2례。치료과정중출현적불량반응균위1～2급，골수억제위최상견적불량반응。림상치료제량체도400 mg/주시병미출현3급이상불량반응，가량호내수。3개월후평개근기료효，5례병정은정，4례출현진전。결론：본연구현시니타주단항연합술후동보방화료대우치료화인악성효질류적불량반응경미，가량호내수。
Objective:The poor prognosis of patients with malignant gliomas (MG) has led to the search for new therapeutic strat-egies. Recently, nimotuzumab has been studied as a new anti-EGFR-receptor humanized monoclonal antibody in patients with MG, who showed improvement of outcome and good tolerability. We conducted phase I of our study to determine the toxicity, tolerated dose, and clinical feasibility of nimotuzumab in combination with concurrent chemoradiotherapy for Chinese MG patients after surgical resection. Methods:Patients with pathologically proven grades 3 and 4 glioma were enrolled in the study. The protocol included infu-sions of nimotuzumab plus standard Stupp schedule (postoperative radiotherapy in a total dose of 60 Gy in combination with daily te-mozolomide). Patients received 6 weekly infusions of nimotuzumab at three levels (100, 200, and 400 mg/week). If none of the first three patients enrolled at a dose level experienced dose-limiting toxicity (DLT), the dose was increased, as appropriate. If DLT was ob-served, another three patients were added to the dose level. Results:Nine patients with MG were enrolled, including 7 with grade 3 MG and 2 with glioblastoma. The treatment was well tolerated, and no evidence of grade 3 or 4 adverse events was detected, even at the highest level (400 mg/week). Grade 1 or 2 myelosuppression was the most common toxicity. Three months after treatment, stable dis-ease occurred in 5 patients, whereas progression disease was observed in 4 patients. Conclusion:Nimotuzumab combined with concur-rent chemoradiotherapy was associated with mild toxicity in Chinese MG patients.