title: [Tumoral dihydropyrimidine dehydrogenase expression and efficacy of 5-fluorouracil plus leucovorin plus UFT therapy in patients with colorectal cancer].
abstract: The purpose of this study was to examine the relation between tumoral expression of dihydropyrimidine dehydrogenase (DPD), the rate limiting enzyme of the degradation pathway 5-fluorouracil (5-FU), and the efficacy of 5-FU based chemotherapy for colorectal cancer. Twenty-eight colorectal cancer patients who had underwent noncurative resection (n = 16) or had developed recurrence (n = 12) were enrolled. All patients were given 5-FU plus leucovorin intravenously and UFT (1 M Tegafur, 4 M Uracil) perorally. The expression levels of the DPD in the primary lesions were determined by the enzyme-linked immunosorbent assay. Group A (n = 10) consisted of one patient with complete response, 4 with partial response, and 5 with no change (time to disease progression (TTP) > = 90 days). Group B (n = 18) consisted of 14 patients with progressive disease and 4 with NC (time to progression, < 90 days). The tumoral DPD levels did not differ between the groups (p = 0.58). There were no effective cases (n = 6) whose tumoral DPD levels were equal to or more than 83.2 U/mg protein (high DPD expression). There were marked overlaps in the DPD levels between the two groups whose DPD levels were less than 83.0 U/mg protein (moderate or low expression). These results suggest that high expression of tumoral DPD would be predictive to failure of fluoropyrimidine-based treatment. However, it is unlikely to set the optimal cutoff value for predicting the efficacy of this type of chemotherapy.
authors.affiliation: Dept. of Surgery, Saitama Medical Center, Saitama Medical School.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ohsawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakada
authors.forename: Masaru
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Inokuma
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirakawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamada
authors.forename: Daijo
authors.initials: D
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D002955:Leucovorin; D005472:Fluorouracil