Central nervous system toxicity of interferon.
Central nervous system toxicity of interferon.
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DOI：
10.1038/bjc.1983.63
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发表时间：
1983-03
影响因子：
8.8
通讯作者：
Lister, T A
中科院分区：
文献类型：
--
作者：
Rohatiner, A Z;Prior, P F;Burton, A C;Smith, A T;Balkwill, F R;Lister, T A
干扰素（IFN）在恶性肿瘤治疗中的潜在作用目前正在评估中。一些中枢神经系统（CNS）毒性，通常表现为嗜睡或意识模糊，已经记录了所有IFN制剂，几乎与剂量和时间表无关（Priestman 1980，Scott等人，1981），并且当通过连续静脉内输注施用高剂量的源自Namalwa淋巴母细胞样细胞的IFN（HuIFN-aN）时，其显示为主要的剂量限制性毒性（Rohatiner等人，1982年）。因此，决定对HuIFN-axN和基因克隆的HuIFN-a2的CNS副作用进行正式研究，以基于用于治疗骨髓性白血病的I期研究选择的剂量给予。本研究的结果包括临床检查、连续脑电图（EEG）、眼球运动调查、代谢功能生化测试以及血清和脑脊液IFN水平，如下所示。研究了11名患者，其中8名为前瞻性研究（4例急性髓性白血病（AML），2例慢性髓性白血病（CML），1例慢性淋巴细胞白血病（CLL）和1例滤泡性淋巴瘤）和3例回顾性（AML）。后者被包括在内，因为不可避免地有限的数据有关脑脊液IFN浓度。七名患者接受HuIFN-axN（Wellcome Research Laboratories，比活性：2.13 × 108 u. mg-蛋白质）。四名患者用基因克隆的HuIFN-CX 2（Schering Plough，比活性：> 2 X IO 8 u. mg-蛋白质）。所有患者均接受100 × 106 u。m-2/天，连续静脉输注7天，除了一名患者以一半剂量接受第二个周期，另一名患者（在I期研究中）接受200 × 106 μ m-2/天，持续5天。
The potential role of Interferon (IFN) in the treatment of malignant disease iscurrently being evaluated. Some central nervous system (CNS) toxicity, usually manifested by drowsiness or confusion has been recorded with all IFN preparations, almost regardless of the dose and schedule (Priestman 1980, Scott et al., 1981) and it was shown to be the major dose-limiting toxicity when high doses of IFN derived from Namalwa lymphoblastoid cells(HuIFN-aN) were administered by continuous iv infusion (Rohatiner et al., 1982). It was therefore decided to undertake a formal study of the CNS side effects of HuIFN-axN and gene-cloned HuIFN-a2, given at the dose selected on the basis of Phase I Studies for the treatment of myelogenous leukaemia. The results of this study comprising clinical examination, serial electroencephalography (EEG), investigation of eye movements, biochemical tests of metabolic function and serum and cerebrospinal fluid IFN levels are presented below.Eleven patients were investigated, 8 prospectively (4 acute myelogenous leukaemia (AML), 2 chronic myeloid leukaemia (CML), 1 chronic lymphocytic leukaemia (CLL) and 1 follicular lymphoma) and 3 retrospectively (AML). The latter are included because of the inevitably limited data concerning cerebrospinal fluid IFN concentrations. Seven patients received HuIFN-axN (Wellcome Research Laboratories, specific activity: 2.13 x 108 u. mg-protein). Four patients were treated with gene-cloned HuIFN-CX2 (Schering Plough, specific activity:> 2 x 108u. mg-protein). All patients received 100x 106u. m-2 per day administered by continuous iv infusion for 7 days, with the exception of one patient who received a second cycle at half the dose and another (in the Phase I study) who received 200 x 106 um-2 per day for 5 days.