[Studies on the effect of high-dose methotrexate-citrovorum factor treatment for 89Sr induced osteosarcoma in mice...

We treated mice with 89Sr induced osteosarcoma with HD MTX (high-dose methotrexate) and CF (rescue by citrovorum factor), and observed the results of MTX administration. MTX and CF constantly injected through their tail veins at intervals of 6, 24 hours, respectively. The amont of MTX administered ranged from 60 mg/kg to 2,000 mg/kg, while CF administered totalled 200 mg/kg. To determine their antitumor efficacy, we adopted 3H-thymidine based labelling index and mitotic index as well as microautoradiography, and observed how the tumor proliferation had been prohibited. The anti-tumor efficacy was significant when 500 mg/kg of MTX was administered; there was no significant increase in anti-tumor efficacy even after 1,000, 2,000 mg/kg of MTX had been administered. Rather, the tumor was tending to be healed as time passed by after the administration of MTX being 500 mg/kg. Then we administered 500 mg/kg of MTX and 200 mg/kg of CF twice at intervals of 6 days. After we had administered MTX in combination with CF, we started observing the changing condition of the tumor. As a result, we recognized their significant anti-tumor efficacy. The tumor did not show any indication of serious growth. In view of the above, we concluded that it would be more effective to administer repeatedly an optimum dose of MTX and CF than to administer an ultra-high dose of MTX and CF.