Level of 5-fluorodeoxyuridine 5'-monophosphate in cancerous tissue in patients with gastric cancer under preoperative administration of TS-1. A preliminary study

J Exp Clin Cancer Res. 2005 Sep;24(3):457-62.

Abstract

Metabolizing enzymes such as thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have long been known to be useful for predicting response and outcome in patients receiving 5-fluorouracil (5-FU). However, few studies have examined the cancerous tissue levels of 5-fluorodeoxyuridine 5'-monophosphate (FdUMP), a metabolite of 5-FU that has an important role in inhibiting DNA synthesis. In this study, for the first time to our knowledge, we measured concentrations of FdUMP in tumor specimens and surrounding non-cancerous tissue obtained at operation in 10 patients with gastric cancer who received TS-1 before surgery (80 mg/m2, 3 days). The FdUMP level in the cancerous tissue was significantly higher than that in the non-cancerous tissue (153.0 +/- 85.7 pmol/g tissue vs. 53.0 +/- 47.0 pmol/g tissue)(p = 0.0046). Furthermore, the TS level in tumor was significantly higher than that in non-cancerous tissue (6.362 +/- 5.106 pmol/g tissue vs. 2.092 +/- 2.050 pmol/g tissue) (p = 0.0310). The mean ratios of TS-bound FdUMP to TS and FdUMP concentrations in the cancerous tissues were 45.9% and 2.00%, respectively. Our results demonstrate that in cancerous tissue, TS-1 may produce high FdUMP concentration and suppress about half FdUMP concentration by forming ternary complexes.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Drug Combinations
  • Female
  • Floxuridine / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Oxonic Acid / therapeutic use*
  • Preoperative Care
  • Pyridines / administration & dosage
  • Pyridines / therapeutic use*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / surgery
  • Tegafur / administration & dosage
  • Tegafur / therapeutic use*
  • Thymidylate Synthase / metabolism

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Pyridines
  • Floxuridine
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Thymidylate Synthase