Role of dihydropyrimidine dehydrogenase activity in patients with esophageal cancer.
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme involved in the degradation of 5-FU. DPD activity in peripheral blood mononuclear cells of 30 esophageal cancer patients treated with 5-FU and low-dose CDDP with irradiation was determined at the beginning of each cytostatic cycle, the objective being to determine if DPD activity is related to the occurrence of side-effects and responses to therapy. The DPD activity showed interpatient variability (mean: 325.5 pmol/min/mg protein). 5-FU-related side-effects tended to be registered more frequently in patients with low DPD activity. In particular, nausea occurred in 30.8% of patients in the high DPD activity group but, in 70.6% in those with low DPD activity (p < 0.05). The relationship between the histological response to therapy and DPD activity was nil. We propose that determination of DPD activity prior to initiation of 5-FU-based chemotherapy for patients with esophageal cancer could aid in identifying those at risk for toxicity.
Saeki
Hiroshi
H
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. hsaeki@med.kyushu-u.ac.jp
Ito
Shuhei
S
Futatsugi
Motonori
M
Kimura
Yasue
Y
Ohga
Takefumi
T
Sugimachi
Keizo
K
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D042943:Dihydrouracil Dehydrogenase (NADP); D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000097:blood*
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D002945:Cisplatin; D005472:Fluorouracil