Docetaxel enhances the cytotoxicity of anthracyclines by increasing intracellular drug accumulation

We assessed the combined antitumor activity of docetaxel and doxorubicin (DXR) and tetrahydropyranyladriamycin (THP) using the human breast carcinoma cell lines R-27 and MDA-MB-231. Synergistic antitumor activity was observed for both combined docetaxel and DXR, and docetaxel and THP against R-27 cells when contacted simultaneously. However, only additive effects were observed against MDA-MB-231 cells. Intracellular concentrations of DXR and THP in R-27 cells were significantly increased by docetaxel pretreatment, however, this increase was not observed in MDA-MB-231 cells, which exhibited only additive sensitivity to the treatment. Thus, docetaxel increased the antitumor activity of anthracyclines by increasing their intracellular concentrations.