Objectives: The objectives of this study were to determine the optimum schedule for combination of taxane and platinum agents in human ovarian carcinoma cell lines.
Methods: Cell growth inhibition was determined by the standard MTT assay and an IC(50) was calculated for docetaxel, paclitaxel, cisplatin, and carboplatin in seven human ovarian cancer cell lines (CAOV-3, OVCAR-3, SKOV-3, ES-2, OV-90, TOV-112D, and TOV-21G). The IC(50) was defined as the drug concentration required for a 50% reduction in optical density. Cytotoxicity assays were performed with four sequential combinations of a taxane and a platinum compound. In each combination, cell lines were treated with the appropriate IC(50) of the drugs for varying time increments between 3 and 24 h. Controls were no drug, each agent alone and the combination of both. Results were obtained via manual cell counting with a hemocytometer.
Results: The inhibitory concentration to achieve 50% cell death (IC(50)) was determined for each compound in each cell line. The IC(50) ranged from 0.8 to 1.7 nM, 0.7 to 1.8 nM for docetaxel and paclitaxel, respectively, and 17.4 to 25.7 microM, 15.1 to 25.7 microM for cisplatin and carboplatin, respectively.
Conclusion: In this study the combination of docetaxel plus cisplatin was considerably more active in vitro than any of the other taxane plus platinum agent combinations evaluated in the panel of human ovarian cancer cell lines. In vitro activity was similar to previously report clinical studies comparing taxane and platinum combination regimens. This suggests the combination of docetaxel with cisplatin will have enhanced clinical activity compared to the paclitaxel plus carboplatin regimen.