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

BACKGROUND. The combination of paclitaxel and cisplatin is standard for pat ients with newly diagnosed epithelial ovarian carcinoma; The role of anothe r taxane, docetaxel, currently is being studied. Due to its milder nonhemat ologic 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 ovaria n carcinoma in vitro, and to assess the type of interaction, if any. METHODS. Sensitivity to carboplatin and the concomitant use of a taxane and carboplatin was studied in 4 ovarian carcinoma cell lines using the 96-wel l 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 da ta to the linear quadratic equation. Synergism was studied by the area unde r the survival curve ratios (AUC ratios), obtained by numeric integration. The AUC ratio and the surviving fraction (SF) value after the administratio n of taxane alone were compared using the Student t test for paired data. RESULTS, The IC50 values for carboplatin were between 0.5-1.6 mu g/mL; ther e was only a 3.2-fold difference between individual cell lines. Carboplatin administered concomitantly with a taxane had either an additive or supra-a dditive growth inhibitory effect on all four ovarian carcinoma cell lines. A supra-additive effect occurred after simultaneous exposure of the cells t o 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 combinati on 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 concen tration in the other two cell lines (UT-OC-S and SK-OV-3). CONCLUSIONS. Carboplatin has a synergistic effect when used with paclitaxel or docetaxel. A supra-additive effect is achieved with a wider range of pa clitaxel concentrations than docetaxel concentrations. Cancer 1999;86:2066- 73. (C) 1999 American Cancer Society.