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 inhibitio n of microtubule depolymerisation and accumulates cells in their G2/M-phase , which is a highly sensitive phase of the cell cycle. The present study wa s designed to test the hypothesis that this property may lead to an enhance d effect of ionizing radiation on tumors. In a first experiment subcutaneou s MA 16/C murine tumors, which are highly responsive to docetaxel, were tre ated intravenously with 45 mg/kg docetaxel and 6 hours later irradiated wit h 500 cGy (day 1). The pretreatment time of 6 hours resulted in a maximum m itotic index at the time of irradiation. On day 3 and 5, an additional 500 cGy was administered, without pretreatment with docetaxel. In a second expe riment 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 gr owth delay (Td) was found among docetaxel treated mice and combinedly treat ed animals. Though a radiation dose of 1500 cGy on its own had no antitumor al effect on MA 16/C tumors, there was a marked tendency (but not statistic ally significant) to a better effect with the combined therapy in compariso n with docetaxel alone (in experiment 1). Further studies with more radiose nsitive tumors are warranted to determine the putative role of M-phase arre st on the radiosensitizing properties of docetaxel.