Optimal treatment regimens for 5'-deoxy-5-fluorouridine, with or without (E)-5-(2-bromovinyl)-2'-deoxyuridine, against various tumors in mice.
The antitumor activity of 5'-deoxy-5-fluorouridine (DFUR), a prodrug of 5-fluorouracil (5-FU), is markedly enhanced if DFUR treatment is combined with (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU). Combined oral administration of DFUR (10 mg/kg) and BVDU (10 mg/kg) three times (every 3 h) per day for 5 days afforded greater antitumor activity than a single dose of DFUR (300 mg/kg/day) for 5 days in mice bearing either adenocarcinoma 755 or Lewis lung carcinoma, while in the colon 26 system the antitumor effects of both treatment regimens were equivalent. Thus, a low-dose regimen of DFUR when combined with BVDU provides a similar or greater antitumor activity than a high-dose regimen of DFUR that is not combined with BVDU. The area under the curve of plasma 5-FU following a treatment with the combination of DFUR (10 mg/kg) and BVDU (10 mg/kg) was equal to that following DFUR (300 mg/kg) treatment.
Iigo
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo.
Miwa
M
M
De Clercq
E
E
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D004359:Drug Therapy, Combination; D005467:Floxuridine / Q000627:therapeutic use*; D005472:Fluorouracil / Q000097:blood; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D010430:Pentosyltransferases / Q000378:metabolism; D011355:Prodrugs / Q000627:therapeutic use; D057845:Pyrimidine Phosphorylases
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011355:Prodrugs; D005467:Floxuridine; C020235:brivudine; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D001973:Bromodeoxyuridine; D005472:Fluorouracil; C025034:doxifluridine