A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxy benzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice

Y. Nio, H. Kimura, M. Tsubono, C. C. Tseng, K. Kawabata, Y. Masai, H. Hayashi, S. Araya, C. Meyer, M. Fukumoto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFU R and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity. These results suggest that Ro09-1390 may be a more beneficial antitumor fluoropyrimidine, at least in the treatment of gastric cancer, than 5'-DFUR.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalAnti-cancer drugs
Volume3
Issue number4
Publication statusPublished - 1992 Jan 1

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

Fingerprint

Dive into the research topics of 'A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxy benzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice'. Together they form a unique fingerprint.

Cite this