Solomon Maria Teresa, Miranda Nederlay, Jorrín Eugenia, Chon Ivonne, Marinello Jorge Juan, Alert José, Lorenzo-Luaces Patricia, Crombet Tania
Calixto García Hospital; Havana, Cuba.
National Institute of Oncology and Radiobiology; Havana, Cuba.
Cancer Biol Ther. 2014 May;15(5):504-9. doi: 10.4161/cbt.28021. Epub 2014 Feb 12.
Nimotuzumab, a humanized antibody targeting epidermal growth factor receptor, has potent anti-proliferative, anti-angiogenic, and pro-apoptotic effects in vitro and in vivo. It also reduces the number of radio-resistant CD133(+) glioma stem cells. The antibody has been extensively evaluated in patients with advanced head and neck, glioma, lung, esophageal, pancreatic, and gastric cancer. In this single institution experience, 35 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with irradiation and 200 mg doses of nimotuzumab. The first 6 doses were administered weekly, together with radiotherapy, and then treatment continued every 21 days until 1 year. The median number of doses was 12, and the median cumulative dose was thus 2400 mg of nimotuzumab. The most frequent treatment-related toxicities were increase in liver function tests, fever, nausea, anorexia, asthenia, dizziness, and tremors. These adverse reactions were classified as mild and moderate. The median survival time was 12.4 mo or 27.0 mo for patients with GBM or AA patients, respectively, who received curative-intent radiotherapy in combination with the antibody. The survival time of a matched population treated at the same hospital with irradiation alone was decreased (median 8.0 and 12.2 mo for GBM and AA patients, respectively) compared with that of the patients who received nimotuzumab and curative-intent radiotherapy. We have thus confirmed that nimotuzumab is a very well-tolerated drug, lacking cumulative toxicity after maintenance doses. This study, in a poor prognosis population, validates the previous data of survival gain after combining nimotuzumab and radiotherapy, in newly diagnosed high-grade glioma patients.
尼妥珠单抗是一种靶向表皮生长因子受体的人源化抗体，在体外和体内均具有强大的抗增殖、抗血管生成和促凋亡作用。它还能减少放射抗性CD133(+)胶质瘤干细胞的数量。该抗体已在晚期头颈癌、胶质瘤、肺癌、食管癌、胰腺癌和胃癌患者中进行了广泛评估。在这项单机构经验研究中，35例间变性星形细胞瘤（AA）或多形性胶质母细胞瘤（GBM）患者接受了放疗和200mg剂量的尼妥珠单抗治疗。前6剂每周给药一次，与放疗同时进行，然后每21天继续治疗一次，直至1年。给药剂量中位数为12剂，因此尼妥珠单抗的累积剂量中位数为2400mg。最常见的治疗相关毒性是肝功能检查指标升高、发热、恶心、厌食、乏力、头晕和震颤。这些不良反应被分类为轻度和中度。接受根治性放疗联合该抗体治疗的GBM或AA患者的中位生存时间分别为12.4个月或27.0个月。与接受尼妥珠单抗和根治性放疗的患者相比，在同一家医院仅接受放疗的匹配人群的生存时间缩短（GBM和AA患者的中位生存时间分别为8.0个月和12.2个月）。因此，我们证实尼妥珠单抗是一种耐受性非常好的药物，维持剂量后无累积毒性。这项针对预后较差人群的研究验证了先前关于新诊断的高级别胶质瘤患者联合使用尼妥珠单抗和放疗后生存获益的数据。
