Impact of 5-fluorouracil metabolizing enzymes on chemotherapy in patients with resectable colorectal cancer

• Published in: Oncology reports Vol. 32; no. 3; pp. 887 - 892
• Main Authors: OCHIAI, TAKUMI, UMEKI, MASAHIKO, MIYAKE, HIROSHI, IIDA, TATSUMI, OKUMURA, MINORU, OHNO, KAZUHIDE, SAKAMOTO, MASASHI, MIYOSHI, NOBUKAZU, TAKAHASHI, MASAHIKO, TSUMURA, HIDENORI, TOKUNAGA, YUKIHIKO, NAITOU, HARUHIKO, FUKUI, TAKUJI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-09-2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: 5-fluorouracil; adjuvant chemotherapy; Administration, Oral; Adult; Age; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacology; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cancer therapies; Chemotherapy; Classification; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - pathology; Confidence intervals; Dehydrogenases; dihydropyrimidine dehydrogenase; Dihydrouracil Dehydrogenase (NADP) - metabolism; Drug therapy; Enzymes; Female; Fluorouracil; Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Gastric cancer; Gender; Genetic aspects; Health aspects; Humans; Leucovorin - administration & dosage; Leucovorin - pharmacology; Lymphatic system; Male; Medical prognosis; Metabolites; Metastasis; Middle Aged; Multivariate analysis; Oncology; orotate phosphoribosyltransferase; Orotate Phosphoribosyltransferase - metabolism; Patients; Prospective Studies; Ratios; Survival Analysis; Japan
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2014.3299

Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin (LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum χ2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.