[Enhancement of hyperthermochemotherapy with hypoxic cell radiosensitizers]

Hyperthermochemotherapy with hypoxic cell radiosensitizers has been carried out using human gastric cancer xenotransplanted into the nude mouse. Misonidazole (MIS) and metronidazole (MTR), hypoxic cell radiosensitizers, were administered singularly or in combination with an ip dose of 500 mg/kg each, and after 60 minutes, an ip dose of MMC of 2.0 mg/kg was given. Subsequently, hyperthermia was applied, twice at a 48-hour interval, by a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. The antitumor activity of hyperthermia with MTR was similar to that of hyperthermia alone, whereas hyperthermia with MIS surpassed hyperthermia alone, at 0.03237 less than p less than 0.05038. Hyperthermia combined with MIS and MMC enhanced the antitumor effects, as compared to hyperthermia with MMC, and with MMC plus MTR. Tumor volumetric tripling times in case of MMC plus heat, MTR, MMC plus heat, and MIS, MMC plus heat were about 229, 213, and 398 hours, respectively, compared to about 110 hours in the control and 160 hours in the case of hyperthermia alone. Thus, these data suggest that the antitumor efficacy of hyperthermochemotherapy with MIS may be the result of a synergistic phenomenon of thermo-chemosensitization.