Enhanced therapeutic efficacy of 5'deoxy-5-fluorouridine in 5-flourouracil resistant head and neck tumours in relation to 5-fluorouracil metabolizing enzymes

G. J. Peters, B. J M Braakhuis, E. A. De Bruijn, E. J. Laurensse, M. Van Walsum, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

Four human head and neck xenograft (HNX) tumour lines grown in nude mice and two murine colon carcinomas (Colon 26 and 38) were tested for their sensitivity to 5-fluorouracil (5-FU) and its prodrug 5'deoxy-5-fluorouridine (Doxifluridine, 5'd-FUR). 5-FU sensitivity at the maximum tolerated dose (MTD) showed the following pattern: HNX-DU <HNX-KE=HNX-E=HNX-G <Colon 26 > HNX-DU > HNX-G > HNX-E > HNX-KE >> Colon 38; of 5-FU to FdUMP via FUdR: Colon 26 > HNX-DU=HNX-KE > HNX-E > HNX-G=Colon 38; and that of 5-FU to FUMP catalysed by orotate phosphoribosyl transferase (OPRT); Colon 26 ≥ Colon 38 > HNX-KE > HNX-E=HNX-DU=HNX-G. Only those tumours with a relatively high activity of OPRT were sensitive to 5'd-FUR. Colon 26, which has a very high rate of pyrimidine nucleoside phosphorylase, showed a relatively high increase in the therapeutic efficacy. It is concluded that a low rate of pyrimidine nucleoside phosphorylase is enough to convert 5'd-FUR to 5-FU; further anabolism of 5-FU catalysed by OPRT may be limiting and explain the differential sensitivity.

Original languageEnglish (US)
Pages (from-to)327-334
Number of pages8
JournalBritish Journal of Cancer
Volume59
Issue number3
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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