The effect of pretreatment with docetaxel (taxotere; RP 56976) on irradiated subcutaneous MA 16/C murine tumors.

Docetaxel (taxotere; RP 56976) is twice as potent as taxol in the inhibition of microtubule depolymerisation and accumulates cells in their G2/M-phase, which is a highly sensitive phase of the cell cycle. The present study was designed to test the hypothesis that this property may lead to an enhanced effect of ionizing radiation on tumors. In a first experiment subcutaneous MA 16/C murine tumors, which are highly responsive to docetaxel, were treated intravenously with 45 mg/kg docetaxel and 6 hours later irradiated with 500 cGy (day 1). The pretreatment time of 6 hours resulted in a maximum mitotic index at the time of irradiation. On day 3 and 5, an additional 500 cGy was administered, without pretreatment with docetaxel. In a second experiment the radiation dose was given similarly, but pretreated with 15 mg/kg docetaxel. In both experiments, a prolonged increase of lifespan (%ILS) and a tumor growth delay (Td) was found among docetaxel treated mice and combinedly treated animals. Though a radiation dose of 1500 cGy on its own had no antitumoral effect on MA 16/C tumors, there was a marked tendency (but not statistically significant) to a better effect with the combined therapy in comparison with docetaxel alone (in experiment 1). Further studies with more radiosensitive tumors are warranted to determine the putative role of M-phase arrest on the radiosensitizing properties of docetaxel.