Doz F, Berens M E, Dougherty D V, Rosenblum M L
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
J Neurooncol. 1991 Aug;11(1):27-35. doi: 10.1007/BF00166994.
Carboplatin has lower nephro- and neurotoxicities and better penetration into brain tissue than cisplatin. If carboplatin has comparable cytotoxicity against glioma cells, it might have a therapeutic advantage in the treatment of malignant gliomas. Using an assay of colony-forming efficiency, we compared the cytotoxicity of these two drugs in human glioma cell lines SF-126, SF-188, U87-MG, and U251-MG. The experiments were designed so that the product of in vitro drug concentration (C) and time (T) would encompass the same range of values as the C x T of the ultrafilterable platinum plasma fraction as determined by pharmacokinetic studies in man. The in vitro stability of the drugs was evaluated by measuring the cytotoxicity of aged drugs with a microculture tetrazolium assay. Cisplatin and carboplatin were both stable during the 2-h treatment. The cytotoxic activities of these drugs at clinically achievable levels of drug exposure were of the same order of magnitude. These results, in conjunction with the lower nephro- and neurotoxicities of carboplatin, the higher platinum levels in brain tissue after treatment with carboplatin, and the encouraging results of carboplatin in the clinical treatment of brain tumors that have been demonstrated in other studies, suggest that carboplatin might be preferable to cisplatin in the treatment of patients with malignant glioma.
与顺铂相比，卡铂具有较低的肾毒性和神经毒性，并且对脑组织的穿透力更强。如果卡铂对胶质瘤细胞具有相当的细胞毒性，那么它在治疗恶性胶质瘤方面可能具有治疗优势。我们使用集落形成效率测定法，比较了这两种药物在人胶质瘤细胞系SF-126、SF-188、U87-MG和U251-MG中的细胞毒性。实验设计使得体外药物浓度（C）和时间（T）的乘积涵盖与人体药代动力学研究确定的可超滤铂血浆分数的C×T相同的值范围。通过用微量培养四唑盐测定法测量老化药物的细胞毒性来评估药物的体外稳定性。顺铂和卡铂在2小时治疗期间均稳定。这些药物在临床可达到的药物暴露水平下的细胞毒性活性处于相同的数量级。这些结果，结合卡铂较低的肾毒性和神经毒性、卡铂治疗后脑组织中较高的铂水平以及其他研究中已证明的卡铂在脑肿瘤临床治疗中的令人鼓舞的结果，表明在治疗恶性胶质瘤患者时，卡铂可能比顺铂更可取。
