Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures

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Abstract
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.