Hyperthermia enhances the inhibition of tumor growth by 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil (1:4) in tumors in mice and humans.
The cytotoxicity of several antitumor drugs is enhanced by hyperthermia (HT). Using mouse Sarcoma-180 (S-180) tumors, the authors examined the effects of 5-fluorouracil (5-FU) and a combined oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) and uracil in a molar ratio of 1:4 (UFT), in combination with HT. The antitumor effect of 5-FU was not enhanced significantly by HT. Growth inhibition by UFT plus HT was significantly greater than that by UFT alone, whereas inhibition by UFT alone was significantly greater than that by 5-FU. The intracellular metabolism of 5-FU and FT in whole homogenates of S-180 cells, human tumor cell lines (SC-2 and Lu-99), and five fresh human tumor tissues also was investigated. Conversion of FT to 5-FU, phosphorylation, and degradation of 5-FU were assayed with [3H]FT or [3H]5-FU, and the products were separated by thin-layer chromatography. The conversion of FT to 5-FU and the phosphorylation of 5-FU were more rapid at 43 degrees C than at 37 degrees C, whereas the degradation of 5-FU to 2-fluoro-beta-alanine remained unchanged. This acceleration of the active metabolism of FT and 5-FU may be one explanation for the enhanced effect of UFT by HT.
Emi
Y
Y
Cancer Center of Kyushu University Hospital, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kohnoe
S
S
Yoshida
M
M
Takahashi
I
I
Maehara
Y
Y
Sugimachi
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D010766:Phosphorylation; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D005641:Tegafur; C025404:3-FT; D005472:Fluorouracil