Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro.

Abstract

The combination of paclitaxel and cisplatin is standard for patients with newly diagnosed epithelial ovarian carcinoma. The role of another taxane, docetaxel, currently is being studied. Due to its milder nonhematologic toxicity carboplatin increasingly is being substituted for cisplatin in taxane-based combinations. The purpose of this study was to compare the combination of carboplatin-paclitaxel with carboplatin-docetaxel in ovarian carcinoma in vitro, and to assess the type of interaction, if any. Sensitivity to carboplatin and the concomitant use of a taxane and carboplatin was studied in 4 ovarian carcinoma cell lines using the 96-well plate clonogenic assay. Chemosensitivity was expressed as the IC50 value (i.e., the drug concentration causing 50% inhibition of clonogenic survival). IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation. Synergism was studied by the area under the survival curve ratios (AUC ratios), obtained by numeric integration. The AUC ratio and the surviving fraction (SF) value after the administration of taxane alone were compared using the Student t test for paired data. The IC50 values for carboplatin were between 0.5-1.6 microgram/mL; there was only a 3.2-fold difference between individual cell lines. Carboplatin administered concomitantly with a taxane had either an additive or supra-additive growth inhibitory effect on all four ovarian carcinoma cell lines. A supra-additive effect occurred after simultaneous exposure of the cells to carboplatin at all tested paclitaxel concentrations in three of four cell lines (UT-OC-3, UT-OC-5, and SK-OV-3). The carboplatin-docetaxel combination had a supra-additive effect at the two highest docetaxel concentrations in two cell lines (UT-OC-4 and UT-OC-5) and at the highest docetaxel concentration in the other two cell lines (UT-OC-3 and SK-OV-3). Carboplatin has a synergistic effect when used with paclitaxel or docetaxel. A supra-additive effect is achieved with a wider range of paclitaxel concentrations than docetaxel concentrations.