Exprerimental Studies on Hyperthermia Combined with Anticancer Chemotherapy In Vivo

Abstract

Anti-tumor effects of 5-FU, FT-207, and FT-207 + uracil against Meth A fibrosarcoma and Sarcoma-180 with two repetitions of 43°C hyperthermia were examined in vivo, in BALB/c mice.
The anti-tumor effect was evaluated in terms of tumor growth inhibition by measuring the tumor size for 7 days, monitoring drug concentrations with HPLC and GC, and histopathological study. Additionally, decomposition from FT-207 to 5-FU by heat was tested at 37°C and 43°C.
As for the tumor growth inhibition, the combination of hyperthermic treatment and FT-207, and FT-207 + uracil showed a synergistic effect, but 5-Fu not, to the both cell lines. With hyperthermic treatment, FT-207 + uracil inhibited tumor growth significantly (p<0.05) more effectively than FT-207. After the second hyperthermic treatment, a slightly lowered tumor response to each of drugs was also observed. After the first hyperthermic treatment, increase in the drug concentrations of FT-207 + uracil and FT-207 was observed, while, there was a substantial significant decrease in that of 5-FU. After the second application of hyperthermic treatment, the concentrations of all the drugs decreased. Pathologically, tumor revealed severe congestion under the treatment of hyperthermia. As for the decomposition from FT-207 to 5-FU by heat, a slight amount of FT-207 changed into 5-FU.
In conclusion, hyperthermia in conjunction with drug therapy is considered to be effective as a cancer treatment. However, it has a tendency of being influenced by the membrane transport systems of the chemotherapeutic agents. And it is assumed that the frequent combination of the two kinds of treatment contradict the chemotherapeutic effect due to decrease the drug concentration by hyperthermia.