IN-VITRO CONCURRENT PACLITAXEL AND RADIATION OF 4 VULVAR SQUAMOUS-CELL CARCINOMA CELL-LINES

BACKGROUND, The antitubule agent paclitaxel causes a cell cycle blocka ge in the most radiosensitive part of the cell cycle, the G(2)/M phase . The possible radiosensitizing effect of paclitaxel was tested in fou r vulvar (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and UM-SCV-4) squamous cell carcinoma (SCC) cell lines. METHODS, A SG-well plate clonogenic assay was performed with paclitaxel and radiation, both separately and conco mitantly. Survival data were fitted to the linear quadratic model. The area under the curve, equivalent to the mean inactivation dose (D), w as obtained by numerical integration. The effect of paclitaxel on radi osensitivity 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 surv ival. The AUC values of the cell lines were 1.9 to 2.9 gray. A full ad ditive effect was observed when paclitaxel and radiation were administ ered concurrently; however, a supra-additive effect never occurred. Th e type of paclitaxel radiation interaction was not affected by the con centration of the drug nor did the type of interaction vary between ce ll lines studied. CONCLUSIONS, Paclitaxel and radiation used concomita ntly 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 investi gation.