The study was designed to determine whether the improvement in the therapeutic ratio of radiotherapy by indomethacin, a potentiator of tumor radioresponse through immunostimulation, can be improved further by combining it with WR-2721, a potent radioprotector of normal tissue. Mice bearing the syngeneic sarcoma FSA (8 mm) in the leg were treated with single graded doses of γ rays to the tumor or with γ rays plus indomethacin, WR-2721, or both. The effect of these compounds was assessed on local tumor control, radiation-caused hair loss, and radiation-induced leg contracture. Indomethacin increased local tumor control by a factor of 1.7, a value that was not influenced significantly by the addition of WR-2721. Indomethacin did not affect radiation-induced hair loss or radiation-induced leg contracture, whereas WR-2721 protected against them by factors of 1.4 and 1.5, respectively. These protection factors were not influenced by the addition of indomethacin. Thus the combination of indomethacin and WR-2721 can increase the therapeutic ratio of radiotherapy more than either drug given alone.

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