Dihydropyrimidine dehydrogenase-related enzymes predict efficacy and adverse reactions of UFT1+cisplatin neoadjuvant chemotherapy for gastric cancer.
Dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP) are metabolic enzymes of fluoropyrimidine. UFT containing uracil (U) and Tegafur is the first reported DPD-inhibitory fluoropyrimidine. To clarify the significance of the enzyme activities, we examined the relationships between the effects and adverse reactions, and DPD and DHP activities in gastric cancer treated with UFT1+cisplatin neoadjuvant chemotherapy. Twenty-five gastric cancer patients were administered UFT at 370 mg/m(2)/day for 21 days and cisplatin at 15 mg/m(2)/day for 2 days. Dihydrouracil (DU) and U levels in the urine and DPD activities in the resected tumors were measured. Chemotherapeutic effects were classified histologically into non-responder and responder groups. The responder group accounted for 48% of the patients. All six patients with high DPD activities (> or = 0.08 nmol/min/ww) belonged to the non-responder group and 11 of 19 patients with low DPD activities (<0.08 nmol/min/ww) belonged to the responder group; the difference was significant (p=0.0435). Adverse reactions to UFT occurred in four patients, all of whom were among the six patients with abnormal DU/U values. The incidence of UFT adverse reactions was estimated at 67%. In conclusion, the measured levels of DPD-related enzyme activities appear to be significant for predicting the effects and adverse reactions to chemotherapy.
Takiguchi
Nobuhiro
N
Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba City 260-8670, Japan. takiguchi@ho.chiba-u.ac.jp
Koda
Keiji
K
Ooshima
Hirokazu
H
Oda
Kenji
K
Suzuki
Hirofumi
H
Ishii
Rumiko
R
Miyazaki
Masaru
M
D000581:Amidohydrolases / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP); D005743:Gastrectomy; D006801:Humans; D010088:Oxidoreductases / Q000378:metabolism*; D011237:Predictive Value of Tests; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000652:urine
C007419:dihydrouracil; D005641:Tegafur; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D000581:Amidohydrolases; C020047:dihydropyrimidinase; D002945:Cisplatin