Enhanced antitumor effect of 5'-deoxy-5-fluorouridine by oral administration with L-cysteine.
When given orally in combination with L-cysteine, 5'-deoxy-5-fluorouridine (DFUR) brought about a significant reduction in the growth of adenocarcinoma 755 and a significant prolongation of life-span in mice bearing Lewis lung carcinoma without increased toxicity to the host as compared with DFUR alone, though L-cysteine alone did not show an appreciable antitumor activity. Moreover, the combination of DFUR and L-cysteine resulted in a marked retardation of growth of human colon tumor LS174T transplanted into nude mice. Thus, the potency of DFUR was increased by L-cysteine. Pharmacokinetic studies revealed that after DFUR administration, plasma DFUR and 5-fluorouracil (5-FU) levels rapidly declined, but that, in the combination with L-cysteine, the plasma clearances of DFUR and 5-FU were slowed down considerably. In the tumor, DFUR and 5-FU levels were similar to those in the plasma. Such a prolongation of DFUR and 5-FU levels in plasma and tumor may produce the enhancement of antitumor effect seen with the combination of DFUR and L-cysteine.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Nakajima
Y
Y
Araki
E
E
Hoshi
A
A
D000230:Adenocarcinoma / Q000188:drug therapy; D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000188:drug therapy; D003545:Cysteine / Q000494:pharmacology*; D004357:Drug Synergism; D005467:Floxuridine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005472:Fluorouracil / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice
D005467:Floxuridine; D003545:Cysteine; D005472:Fluorouracil; C025034:doxifluridine