title: Dose response relationship of methotrexate in combination with cisplatin in murine bladder cancer.
abstract: 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 controlling 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 C3H/HE female mice were injected in the hind limb with 7.5 X 10(4) 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), MTX32 mg, MTX50 mg, MTX80 mg, DDP + MTX32, MTX50 + Leucovorin, MTX80 + Leucovorin, DDP + MTX50 + Leucovorin, DDP + MTX80 + Leucovorin. The combination of MTX50 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 MTX. No toxicity was observed even when high doses of MTX were used.
authors.affiliation: Department of Urology, University of Tennessee, Memphis.
authors.forename: M
authors.initials: M
authors.lastname: Brausi
authors.forename: A
authors.initials: A
authors.lastname: Blatnik
authors.forename: M S
authors.initials: MS
authors.lastname: Soloway
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005200:FANFT; D005260:Female; D002955:Leucovorin / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D005200:FANFT; D002945:Cisplatin; D002955:Leucovorin; D008727:Methotrexate