In vitro evaluation of dose-response curve for paclitaxel in breast cancer

Background  The dose-response curve for anticancer agents cannot be evaluated by studying patients directly. To investigate individual differences in the dose-response curve for paclitaxel in breast cancer, we utilized the histoculture drug response assay (HDRA) technique. as]Materials and Methods: Twenty specimens obtained from breast cancer patients who underwent surgical resection were used in this study. The inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve, using non-linear least squares analysis with the fitting equation y=A(l-l/(l+exp(B(x-log(C))))), where A denotes maximal response; B, slope factor; and C, ED50. Results  A dose-response curve was obtained in all tumors. The mean value (±SD) of maximum response, slope factor, and ED50 were 90.2±5.5 %, 9.4 ± 4.3, and 36.8 ± 17.2 μg/g/ml, respectively. The slope factor was higher in nuclear grade 3 tumors compared with nuclear grade 1 and 2 tumors. Conclusion  An individual dose-response curve for paclitaxel in breast cancer can be obtained using the HDRA technique. Nuclear grade 3 tumors appeared to have more uniform chemosensitivity to paclitaxel compared with nuclear grade 1 and 2 tumors.