In vitro concurrent paclitaxel and radiation of four vulvar squamous cell carcinoma cell lines

Abstract

BACKGROUND The antitubule agent paclitaxel causes a cell cycle blockage in the most radiosensitive part of the cell cycle, the G2/M phase. The possible radiosensitizing effect of paclitaxel was tested in four vulvar (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and UM-SCV-4) squamous cell carcinoma (SCC) cell lines. METHODS A 96-well plate clonogenic assay was performed with paclitaxel and radiation, both separately and concomitantly. Survival data were fitted to the linear quadratic model. The area under the curve, equivalent to the mean inactivation dose (D), was obtained by numerical integration. The effect of paclitaxel on radiosensitivity was measured as the AUC ratio (paclitaxel plus radiation: radiation alone). This ratio was compared with the surviving fraction (SFP) after paclitaxel alone. RESULTS Paclitaxel concentrations of 0.4 to 2.0 nanomolar (nM) caused 1 to 70% inhibition of clonogenic survival. The AUC values of the cell lines were 1.9 to 2.9 gray. A full additive effect was observed when paclitaxel and radiation were administered concurrently; however, a supra-additive effect never occurred. The type of paclitaxel radiation interaction was not affected by the concentration of the drug nor did the type of interaction vary between cell lines studied. CONCLUSIONS Paclitaxel and radiation used concomitantly produced a clear additive effect at all concentrations and in all vulvar carcinoma cell lines tested. Although no supra-additive effect was observed, the additive effect already in nM concentrations could be beneficial in clinical use and, therefore, requires further investigation. Cancer 1996;77:1940-6.