Dihydropyrimidine dehydrogenase activity during long-term adjuvant treatment with oral uracil and tegafur for colorectal cancer.
BACKGROUND
Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for the degradation of 5-fluorouracil. The effect of long-term treatment with oral fluoropyrimidines on DPD activity has not been investigated. This study was conducted to examine changes in DPD activity in peripheral mononuclear cells (PMNC) during long-term treatment with oral uracil and tegafur (UFT) for colorectal cancer.


METHODS
UFT was administered for 5 consecutive days and not administered the next 2 days for 6 months after surgery. PMNC-DPD activity was measured before and 1, 2, 4 and 6 months after starting UFT administration.


RESULTS
In 70 eligible patients, there were no significant variations of PMNC-DPD activity during postoperative administration of UFT for 6 months. Grade 2 or higher adverse events were observed in significantly more patients with low DPD than with high DPD activity (p = 0.018).


CONCLUSIONS
There were no significant variations of PMNC-DPD activity during the postoperative administration of UFT for 6 months. Low PMNC-DPD activity before UFT treatment was considered to be a predicting factor for toxicity.
Sadahiro
Sotaro
S
Department of Surgery, Tokai University School of Medicine, Isehara, Japan. sadahiro@is.icc.u-tokai.ac.jp
Suzuki
Toshiyuki
T
Maeda
Yuji
Y
Ishikawa
Kenji
K
Tanaka
Yoichi
Y
Yasuda
Seiei
S
Kamijo
Akemi
A
Makuuchi
Hiroyasu
H
Murayama
Chieko
C
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D005641:Tegafur / Q000008:administration & dosage; D013997:Time Factors; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP)