Effects of docetaxel in combination with radiation on human head and neck cancer cells (ZMK-1) and cervical squamous cell carcinoma cells (CaSki)

The purpose of this study was to determine, as we did for paclitaxel, the c ytotoxic and radiosensitizing potential of docetaxel in human head and neck cancer cells (ZMK-I), and in cervical squamous cell carcinoma cells (CaSki ). ZMK-I cells were incubated with docetaxel for 3, 9 or 24 hr before irrad iation and 24 hr after irradiation. CaSki cells were incubated with docetax el 24 hr before and after irradiation. For ZMK-I cells, the docetaxel conce ntrations (0.7, 0.7 and 0.35 nM) were determined to obtain approximately eq uivalent cell survival at the different incubation times (3, 9 and 24 hr, r espectively). For CaSki cells, the necessary concentration of docetaxel was 0.07 nM. Radiation doses were given from 0 to 7 Gy, Cell survival was meas ured by a standard clonogenic assay after a 9-day incubation. Flow cytometr y was used to measure the capacity of docetaxel to accumulate cells in the G2/M phase of the cell cycle. We observed a weak accumulation of cells in t he G2/M phase for the ZMK-I cells and a pronounced accumulation for CaSki c ells. For docetaxel incubation before irradiation, the isoeffect enhancemen t ratios for ZMK-I cells determined at the 37% survival level were 1.18, 2. 01, and 2.40 for pre-incubation at 3, 9 and 24 hr, respectively; for CaSki cells the ratio was 1.44. For a docetaxel incubation of 24 hr after irradia tion, the isoeffect enhancement ratios determined at the 37% survival level were 1.54 and 1.17 for the ZMK-I, and CaSki cells, respectively. A radiose nsitizing effect of docetaxel could be demonstrated unambiguously in the tw o cell lines used. In contrast to our previously published results with pac litaxel, docetaxel seems to be a better radiosensitizer than paclitaxel. (C ) 2001 Wiley-Liss. Inc.