Pyrimidine nucleoside phosphorylase and dihydropyrimidine dihydrogenase activities as predictive factors for the efficacy of doxifluridine together with mitomycin C as adjuvant chemotherapy in primary colorectal cancer.
OBJECTIVE
Pyrimidine Nucleoside Phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine) to 5-fluorouracil (5-FU). While this reaction is taking place Dihydropyrimidine Dihydrogenase (DPD) catalyzes 5-FU to inactive molecules. Mitomycin C (MMC) elevates the PyNPase level in tumor cells.


METHODS
We investigated 17 colorectal cancer patients' PyNPase and DPD activities in tumor and normal tissues using an enzyme-linked immunosorbent assay (ELISA) to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR together with MMC as adjuvant chemotherapy.


RESULTS
Six of 17 patients developed experienced a recurrence. Tumor DPD activity of the 6 patients who had a recurrence were higher than those of the 11 patients with no recurrence (p = 0.047). On the other hand, there were no significant differences in both the PyNPase and the PyNPase/DPD (P/D) ratio between the group with recurrence and the group without recurrence. For survival analyses, we designed the cut-off value of tumor PyNPase, DPD and P/D ratio as their median value and classified patients into a higher group and a lower group, but there were no significant differences between the groups.


CONCLUSIONS
The DPD activity in the tumor may be a useful indicator for selecting patients likely respond to 5'-DFUR together with MMC as adjuvant chemotherapy. If tumor DPD is high, we had better select a different anticancer drug.
Nishioka
Masanori
M
Department of Digestive and Pediatric Surgery, Institute of Health Biosciences The University of Tokushima Graduate School, Tokushima, Japan. mnishioka@clin.med.tokushima-u.ac.jp
Miyamoto
Hidenori
H
Kurita
Nobuhiro
N
Higashijima
Jun
J
Yoshikawa
Kouzou
K
Miyatani
Tomohiko
T
Shimada
Mitsuo
M
D000328:Adult; D000368:Aged; D024221:Antineoplastic Protocols; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000032:analysis*; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use*; D010430:Pentosyltransferases / Q000032:analysis*; D011379:Prognosis; D057845:Pyrimidine Phosphorylases; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
D005467:Floxuridine; D016685:Mitomycin; D042943:Dihydrouracil Dehydrogenase (NADP); D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; C025034:doxifluridine