[Antitumor activity and toxicity to the immune system and intestine, of the fluorinated pyrimidines FUra, 5'-DFUR, tegafur and UFT].
Antitumor activity and the toxicities of 5-fluorouracil (FUra) and its depot form derivatives with different mechanisms such as 5'-DFUR, tegafur and UFT, were compared in mice, and the therapeutic indices were measured. 5'-DFUR was less toxic to immune organs and the functions than those by other fluorinated pyrimidines. The therapeutic indices of 5'-DFUR obtained by using parameters of particular side effects, reduction of the number of GM-CFU in the bone marrow, shrinkage of the thymus, functional disorders in the immune systems, were several times higher than those of tegafur and UFT. On the other hand, there were no marked differences in the intestinal toxicities among the compounds. 5'-DFUR was only about two times less toxic on the intestinal tract than tegafur and UFT when the incidence-of diarrhea and damage to the duodenum were compared. These studies suggest that the difference in the mechanisms converting to FUra is a result of the toxicities causing different extent.
Ninomiya
Y
Y
Nippon Roche Research Center, Kamakura City, Kanagawa.
Ryu
M
M
Matsuura
N
N
Fujimoto
K
K
Miwa
M
M
Ishitsuka
H
H
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects; D005260:Female; D005467:Floxuridine / Q000009:adverse effects / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D013154:Spleen / Q000187:drug effects; D005641:Tegafur / Q000009:adverse effects / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects; D014498:Uracil / Q000009:adverse effects / Q000494:pharmacology
D005467:Floxuridine; D005641:Tegafur; D014498:Uracil; C025034:doxifluridine