Methotrexate (MTX) has activity in transitional cell carcinoma (TCC) in man and some have suggested an advantage of high-dose methotrexate versus the standard dose in controling tumor growth and prolonging survival. MBT-2, a poorly differentiated TCC induced by the carcinogen FANFT, is both grossly and histologically similar to human TCC and has been used as an animal model. One hundred twenty C3HIHE female mice were injected in the hind limb with 7.5 × 104 MBT-2 tumor cells. When palpable tumors developed in all animals, therapy was initiated. Animals were randomized into a control group and nine treatment groups as follows: cisplatin (DDP), MTX 32 mg, MTX 50 mg, MTX 80 mg, DDP + MTX 32, MTX 50 + Leucovorin, MTX 80 + Leucovorin, DDP + MTX 50 + Leucovorin, DDP + MTX 80 + Leucovorin. The combination of MTX 50 mg with Leucovorin + DDP and DDP alone were the two most effective regimens in controlling tumor growth and prolonging survival. No statistically significant difference was observed between the group treated by high-dose MTX alone and those treated by low-dose MT X. No toxicity was observed men when high doses of MTX were used.
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