The combination of paclitaxel with cisplatin exhibits antagonism in vitro against human melanoma

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Abstract
The in vitro cytotoxicity of paclitaxel and cisplatin, alone and in combination, was evaluated against the established human melanoma cell line, G361, with either 1 or 24 h asynchronous paclitaxel exposure using the sulforhodamine B assay. As single agent, the mean cisplatin concentration which inhibited G361 cell growth by 50% (IC50) was 10 000 nM for 1 h exposure. IC50 values obtained with 1 and 24 h paclitaxel exposure were, respectively, 63 and 3.8 nM, concentrations clinically achievable. The combination of paclitaxel with cisplatin was found to be antagonistic by the classical isobologram method, independent of drug sequence and of paclitaxel exposure time. The antagonism was significantly more pronounced for the sequence of paclitaxel followed by cisplatin compared with the reverse sequence for both 1 and 24 h paclitaxel exposure time (p < 0.05). Future clinical protocols employing paclitaxel and cisplatin, both active single agents for the treatment of metastatic malignant melanoma, should take into consideration that the combination of the two drugs may result in significant antagonism, irrespective of drug sequence, if administered within a short interval of each other.

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