Dihydropyrimidine dehydrogenase (DPD) activity in gastric cancer tissue and effect of DPD inhibitory fluoropyrimidines.

Abstract

BACKGROUND:

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that catabolizes 5-fluorouracil (5-FU). The effect of DPD inhibitory fluoropyrimidines (DIF) is presumably related to DPD activity. We studied the efficacy of DIF (tegafur + uracil UFT], tegafur + gimeracil + osteracil [S-1 (TS-1)]) relative to DPD activity, with other fluoropyrimidines as controls.

METHODS:

The efficacy of DIF relative to DPD activity was evaluated in 58 gastric cancer patients who received postoperative administration of fluoropyrimidines, consisting of DIF in 42 patients (UFT in 23; S-1 in 19) and non-DIF in 16 patients.

RESULTS:

In patients with low DPD activity (under 40 U/mg protein), curative potential tended to be lower for DIF than for non-DIF, but the survival rate was the same for both. In patients with high DPD activity (40 U/mg protein or more), such a tendency was not detected. In a comparison between those treated with UFT and those treated with S-1, prognosis was better in the latter group, in spite of their predominance of lower curative potentials of B or C. In 27 patients with measurable lesions, a partial response (PR) or higher response occurred in 33% (5/15) of those with low DPD activity, and in 17% (2/12) of those with high DPD activity. In the patients with low DPD activity, non-DIF induced no change (NC) in 17% (16), and progressive disease (PD) in the rest. UFF induced PD in all 5 patients, while S-1 induced a response rate of 44% (7/16), with NC in 25% (4/16). In the patients with high DPD activity, on the other hand, non-DIF (n = 3) and UFT (n = 3) induced PD in all the patients, while S-1 induced PR in 33% (2/6) and NC or a higher response in 67% (4/6).

CONCLUSION:

It is recommended to use S-1 rather than UFF in patients with high DPD activity. Measurement of DPD was useful in drug selection.

• Authors: Hisashi Usuki, Ken Ishimura, Shinichi Yachida, Masanobu Hagiike, Keiichi Okano, Kunihiko Izuishi, Yukihiko Karasawa, Fuminori Goda, Hajime Maeta
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 6 Suppl 1 Pg. 66-70 ( 2003) ISSN: 1436-3291 [Print] Japan
• PMID: 12775023 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• Enzyme Inhibitors
• Pyridines
• S 1 (combination)
• Tegafur
• Uracil
• Oxonic Acid
• Oxidoreductases
• Dihydrouracil Dehydrogenase (NADP)
• Leucovorin
• Fluorouracil

Topics

• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Dihydrouracil Dehydrogenase (NADP)
• Disease Progression
• Drug Combinations
• Enzyme Inhibitors (therapeutic use)
• Fluorouracil (therapeutic use)
• Humans
• Japan
• Leucovorin (therapeutic use)
• Liver Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis
• Oxidoreductases (drug effects, metabolism)
• Oxonic Acid (therapeutic use)
• Peritoneal Neoplasms (drug therapy, secondary)
• Prognosis
• Pyridines (therapeutic use)
• Statistics as Topic
• Stomach Neoplasms (diagnosis, enzymology, mortality)
• Survival Analysis
• Tegafur (therapeutic use)
• Treatment Outcome
• Uracil (therapeutic use)