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Effect of Sequence of Administration of Methotrexate, Leucovorin, and 5-Fluorouracil on Mammary Tumor Growth and Survival in Syngeneic C3H Mice¹

Department of Medicine, Roger Williams General Hospital, Providence 02908, and Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912

The administration of methotrexate (1 mg/kg), leucovorin (1 mg/kg), and (after a 1-hr interval) 5-fluorouracil (50 mg/kg) selectively suppresses antibody production in C3H mice without inhibiting, but even stimulating, cell-mediated immunity. The effect of this regimen, given at weekly intervals, was tested on the growth of recently arising syngeneic C3H/HeJ mammary tumors. Inhibition of growth was found in three types of experiments: (a) when treatment was begun 2 days after tumor implantation, (b) when it was begun 3 weeks after implantation, and (c) when it was begun after surgical enucleation of the tumor. The extent of the effect varied from tumor to tumor, but in all cases tumor incidence or growth was significantly inhibited. Comparison was made between the above regimen and two other sequences of administration of the same drugs, which are only weakly immunosuppressive of antibody production and which do not stimulate cell-mediated immunity. Survival of tumor-bearing mice was greater with the administration of methotrexate, then leucovorin, followed by 5-fluorouracil, than it was with the other two administration schedules.

¹ This work was supported by USPHS Grant CA-13943.

Received 6/27/77. Accepted 9/20/77.

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