Enhancement of antitumor effects of 1-hexylcarbamoyl-5-fluorouracil combined with hyperthermia on Ehrlich ascites tumor in vivo and Nakahara-Fukuoka sarcoma cell in vitro.

1-Hexylcarbamoyl-5-fluorouracil (HCFU) was found to be hydrolyzed to 5-fluorouracil (5-FU) depending on temperature. In this study, the antitumor effects of HCFU with hyperthermia were studied on Ehrlich ascites in tumor-bearing CD-1 mice and Nakahara-Fukuoka sarcoma cells. Concurrently, the change of 5-FU concentration in the Ehrlich tumor was also observed. In vivo, Ehrlich cells were transplanted in the foot pads of mice. HCFU (80 mg/kg) and 5-FU (40 mg/kg) (same molarity) were administered orally on the 3rd, 6th, and 9th days after transplantation and simultaneously hyperthermia (43.5 degrees C, 45 min) was induced. The antitumor effect was evaluated by the tumor volume. On the 9th day after transplantation, HCFU (150 mg/kg) and 5-FU (75 mg/kg) were administered with or without hyperthermia (43.5 degrees C, 45 min) and the tumor tissues were taken for 5-FU concentration analysis. In addition, Nakahara-Fukuoka sarcoma cells were incubated (42 degrees C various times) with our without HCFU and 5-FU (both 1 x 10(-4) M) in vitro. The cytotoxicity was evaluated by colony forming assay. The most effective condition was found to be the combination of HCFU with hyperthermia in vitro and in vivo. The highest 5-FU concentration was observed by the treatment of HCFU combined with hyperthermia in vivo. Hence, HCFU could be clinically useful in thermochemotherapy.