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


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).


CONCLUSIONS
This study indicates that S-1 may be effective even in gastric scirrhous carcinoma with a high level of DPD activity.
Shimizu
Toshio
T
Department of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan. tosshimi@ncc.go.jp
Yamada
Yasuhide
Y
Yasui
Hisateru
H
Shirao
Kuniaki
K
Fukuoka
Masahiro
M
D002293:Adenocarcinoma, Scirrhous / Q000188:drug therapy* / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D005641:Tegafur / Q000627:therapeutic use*
D000906:Antibodies; D004338:Drug Combinations; D011725:Pyridines; D011994:Recombinant Proteins; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil