Improvement in radiotherapy for a murine sarcoma by indomethacin plus WR-2721.
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 gamma rays to the tumor or with gamma 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.
Division of Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
P C
PC
Besa
N R
NR
Hunter
L
L
Milas
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D003286:Contracture / Q000209:etiology; D004359:Drug Therapy, Combination; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011833:Radiation Injuries, Experimental / Q000209:etiology; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000532:radiotherapy*
D004999:Amifostine; D007213:Indomethacin