Clinical efficacy of doxifluridine and correlation to in vitro sensitivity of anticancer drugs in patients with colorectal cancer.
We examined thymidine phosphorylase (TP) expression and sensitivity to anticancer drugs and compared the findings with the efficacy of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine.


METHODS
Patients were enrolled in this study from January 1995 to June 1998 for stages II-III colorectal cancer with curative resection. We conducted sensitivity tests of tumor tissue to 5'-DFUR and 5-fluorouracil (5-FU) using the MTT method, and measured tumor tissue TP levels using enzyme-linked immunosorbent assay (ELISA). From 2 weeks postoperatively, the patients were given oral 5'-DFUR 800 mg/m2/day (5 days administration followed by 2 days discontinuation) for one year and they were followed for 3 years postoperatively.


RESULTS
Of 139 patients registered, 124 were analyzed for the present study. The median 5'-DFUR administration was 362 days and the median total dose was 245.0 g. We compared prognoses in patients with positive and negative 5-FU sensitivity test results. There was a significantly better prognosis in 5-FU sensitivity-positive patients with stage III than that in the sensitivity-negative patients (p = 0.041). We also compared prognoses in patients with positive and negative 5'-DFUR sensitivity test results. There was no significant difference in cases with a cut-off value of 50% (p = 0.055), although patients with 5'-DFUR-positive-sensitivity tended to show longer survival. Patients with stage II and higher TP levels tended to have longer survival than those with lower TP expression, but there was no significant difference between groups (p = 0.087). The prognosis of patients with 5-FU-positive sensitivity and higher TP levels, the positive group, tended to have longer survival than in the negative group, but there was no significant difference between groups (p = 0.083).


CONCLUSIONS
5'-DFUR sensitivity test results and TP values may predict the clinical effects of this drug in colorectal cancer.
Yamaue
Hiroki
H
Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama 641-8510, Japan. yamaue-h@wakayama-med.ac.jp
Tanimura
Hiroshi
H
Kono
Nobuji
N
Aoki
Yozo
Y
Tabuse
Katsuyoshi
K
Uchiyama
Kazuhisa
K
Takifuji
Katsunari
K
Iwahashi
Makoto
M
Tani
Masaji
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005467:Floxuridine / Q000494:pharmacology / Q000627:therapeutic use*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013939:Thymidine Phosphorylase / Q000096:biosynthesis
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D013939:Thymidine Phosphorylase; D005472:Fluorouracil; C025034:doxifluridine