Clinical application of immunoreactivity of dihydropyrimidine dehydrogenase (DPD) in gastric scirrhous carcinoma treated with S-1, a new DPD inhibitory fluoropyrimidine

Anticancer Res. 2005 Jul-Aug;25(4):2997-3001.

Abstract

Background: A highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to immunohistochemically assess DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous carcinoma.

Patients and methods: In this study, the relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy were investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous carcinoma.

Results: The response rate was significantly higher in patients with DPD-positive tumors than in those with DPD-negative tumors in the S-1 group (45.5%, 10.0%: p < 0.05), as compared to the 5-FU group (0%, 5.6%: p = 0.398). According to the median survival time, there was no significant difference between patients with DPD-positive tumors (364 days) and those with DPD-negative tumors (406 days; p = 0.626) in either the S-1 group or the 5-FU group (181 days and 256 days, respectively; p = 0.543).

Conclusion: This study indicates that S-1 may be effective even in gastric scirrhous carcinoma with a high level of DPD activity.

MeSH terms

  • Adenocarcinoma, Scirrhous / drug therapy*
  • Adenocarcinoma, Scirrhous / enzymology*
  • Adult
  • Aged
  • Antibodies / chemistry
  • Antibodies / immunology
  • Antibody Specificity
  • Dihydrouracil Dehydrogenase (NADP) / antagonists & inhibitors
  • Dihydrouracil Dehydrogenase (NADP) / immunology
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Drug Combinations
  • Female
  • Fluorouracil / therapeutic use
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Oxonic Acid / therapeutic use*
  • Pyridines / therapeutic use*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology*
  • Tegafur / therapeutic use*

Substances

  • Antibodies
  • Drug Combinations
  • Pyridines
  • Recombinant Proteins
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil