Enhancement of hyperthermochemotherapy for human gastric cancer in nude mice by thermosensitization with nitroimidazoles

Abstract

Hyperthermia for human gastric cancer xenotransplanted into the hindlegs of nude mice was performed to determine whether misonidazole (MISO) or metronidazole (MTR), derivatives of nitroimidazole, would intensify the antitumour effects of hyperthermia only, or combined with mitomycin C (MMC). MISO, MTR and MMC were given i.p. at doses of 500 mg kg-1, 500 mg kg-1 and 2.0 mg kg-1 respectively, and MISO or MTR was administered 45 min before MMC. Hyperthermia was applied twice at 48 h intervals, by means of a water bath at 43.5 +/- 0.1 degrees C for 23 min. Tumour tripling times following heat alone, MTR plus heat, and MISO plus heat were about 6.7, 8.0 and 7.9 days respectively, compared with 4.6 days for the control, but tumour regression occurred in the heat plus MISO group only. Tumour tripling times for MMC plus heat, MMC plus MTR plus heat, and MMC plus MISO plus heat were 9.6, 11.6 and 17.1 days respectively, compared to 4.6 days for the control and 6.7 days for heat alone. These data suggest that the antitumour activity of MMC plus MISO plus heat is an additive phenomenon.