Combination chemotherapy with cyclophosphamide and ftorafur against advanced L1210 murine leukemia

The antitumor activity of cyclophosphamide (CP) in combination with ftorafur (FT) against advanced L1210 murine leukemia was investigated and compared with the activity of the combination of CP and 5-FU. CP at doses of 200--350 mg/kg was highly active, the most effective dose (% treated/control = 327) being 300 mg/kg. The activity of FT up to the LD10 dose and of 5-FU at 50 mg/kg was minimal (% treated/control less than or equal to 142). Coadministration of 200 mg/kg of FT with 100 mg/kg of CP resulted in an increase in activity as compared with the respective dose of CP alone as did the coadministration of 400 mg/kg of FT with 200 mg/kg of CP; the activities, however, were no better than that resulting from treatment with 300 mg/kg of CP alone. The coadministration of CP and 600 mg/kg of FT resulted in an increase in host toxic reactions and loss of antitumor activity, as did the coadministration of 400 mg/kg of FT with 300 mg/kg of CP. Treatment with FT at 400 or 600 mg/kg 24 hours before or after administration of CP at 200 or 300 mg/kg did not increase the activity over that occurring when the respective combinations of the drugs were coadministered. The activity of the combination of CP with 5-FU at doses previously reported to be synergistic was equal to that observed when mice were treated with 300 mg/kg of CP alone. These data suggest that FT increases the cytotoxicity of CP but that the combination is not synergistic.