The influence of warfarin of levamisole on the incidence of metastases following local irradiation of a solid tumor.
KHT sarcomas were implanted in the right rear legs of C3H mice. An x-ray dose of 6000 rad, delivered in ten equal fractions over 12 days, resulted in 60% local tumor control, but 83% of these mice developed metastases. Three strategies to use the tumoricidal effect of x-radiation and reduce the incidence of metastases were compared. A modification of the fractionation scheme to deliver an initial large fraction of 1800 rad followed by seven 600-rad fractions resulted in a decreased incidence of metastases compared with the same dose delivered in ten equal fractions. The use of warfarin anticoagulation during the ten-fraction course of radiation resulted in a small decrease in the incidence of metastases. Immune stimulation with levamisole, injected subcutaneously every second day during the irradiation, also resulted in a decrease in the incidence of metastases. However, when warfarin or levamisole were combined with the eight-fraction radiation scheme there were fewer metastases than following the ten-fraction scheme. The combination of the eight-fraction radiation course with levamisole also produced a significant increase in primary tumor control. In this treatment regimen, therefore, levamisole appears to act as a radiation sensitizer. An hypothesis to explain this action is proposed.
D000818:Animals; D005260:Female; D007978:Levamisole / Q000494:pharmacology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011379:Prognosis; D011879:Radiotherapy Dosage; D012513:Sarcoma, Experimental / Q000628:therapy*; D014859:Warfarin / Q000494:pharmacology*
D007978:Levamisole; D014859:Warfarin