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

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.