The dihydrouracil/uracil ratios in plasma and toxicities of 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer patients

Background: This study was designed to measure the dihydrouracil (UH2)/uracil (U) ratio in plasma as a surrogate marker for dihydropyrimidine dehydrogenase(DPD) activity and to investigate the relationships of the UH2/U ratios in plasma with the toxicities of 5-fluorouracil (5FU)-based adjuvant chemotherapy and 5-FU plasma concentrations in colorectal cancer patients. Methods: Thirty colorectal cancer patients received adjuvant chemotherapy of leucovorin plus 5-FU after operations. The concentrations of UH2, U and 5-FU were assayed by the high-performance liquid chromatography method. The relationships of the UH2/U ratios with the 5-FU toxicities and 5-FU plasma concentrations were analyzed. Results: There was a negative relationship between the UH2/U ratios and 5-FU plasma concentrations (p < 0.001). 5-FU toxicities had a negative correlation with the UH2/U ratios and a positive correlation with 5-FU plasma concentrations (p < 0.05). Conclusion: The UH2/U ratio in plasma has close correlations with the 5-FU plasma concentration and 5-FU toxicity during chemotherapy, which may highlight the theoretical base of individual therapy for patients with colorectal cancer. Copyright (c) 2007 S. Karger AG, Basel.