Comparative antitumor activity and intestinal toxicity of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine

Jpn J Cancer Res. 1990 Feb;81(2):188-95. doi: 10.1111/j.1349-7006.1990.tb02547.x.


N4-Trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro 09-1390), a prodrug of the cytostatic 5'-deoxy-5-fluorouridine (5'-DFUR), was synthesized with the aim of reducing of the dose-limiting toxicity of 5'-DFUR, which is diarrhea. In mice bearing Lewis lung carcinoma, 5'-DFUR given po produced a substantial amount of 5-fluorouracil (5-FU) in the intestinal tract as well as tumors, where the enzyme pyrimidine nucleoside phosphorylase, essential for conversion of 5'-DFUR to 5-FU, is predominantly located. With the oral administration of Ro 09-1390 only a small amount of 5-FU was formed in the intestine; however, the administration of Ro 09-1390 and 5'-DFUR at the same dose produced similar amounts of 5-FU in tumor tissues. These differences in metabolism were reflected in their toxicity and antitumor efficacy. The administration of 5'-DFUR resulted in damage to the intestinal mucosal membrane and diarrhea in normal mice, whereas Ro 09-1390 was much less toxic to the intestinal tract. As regards antitumor activity, Ro 09-1390 and 5'-DFUR at equivalent doses inhibited the growth of Lewis lung carcinoma to similar extents. Since Ro 09-1390 was much less toxic to the intestinal tract than 5'-DFUR, mice bearing Lewis lung carcinoma could be given Ro 09-1390 daily over a longer period and at a higher dose, resulting in a longer survival time.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Floxuridine / metabolism
  • Floxuridine / pharmacology*
  • Floxuridine / toxicity
  • Fluorouracil / metabolism
  • Fluorouracil / pharmacology
  • Fluorouracil / toxicity
  • Intestines / drug effects*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neoplasms, Experimental / drug therapy
  • Prodrugs / pharmacology*
  • Prodrugs / toxicity


  • Antineoplastic Agents
  • Prodrugs
  • Floxuridine
  • Deoxycytidine
  • Ro 09-1390
  • Fluorouracil
  • doxifluridine