BACKGROUND: This study was designed to measure the dihydrouracil (UH(2))/uracil (U) ratio in plasma as a surrogate marker for dihydropyrimidine dehydrogenase (DPD) activity and to investigate the relationships of the UH(2)/U ratios in plasma with the toxicities of 5-fluorouracil (5-FU)-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 UH(2), U and 5-FU were assayed by the high-performance liquid chromatography method. The relationships of the UH(2)/U ratios with the 5-FU toxicities and 5-FU plasma concentrations were analyzed. RESULTS: There was a negative relationship between the UH(2)/U ratios and 5-FU plasma concentrations (p <0.001). 5-FU toxicities had a negative correlation with the UH(2)/U ratios and a positive correlation with 5-FU plasma concentrations (p < 0.05). CONCLUSION: The UH(2)/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 2007 S. Karger AG, Basel.
BACKGROUND: This study was designed to measure the dihydrouracil (UH(2))/uracil (U) ratio in plasma as a surrogate marker for dihydropyrimidine dehydrogenase (DPD) activity and to investigate the relationships of the UH(2)/U ratios in plasma with the toxicities of 5-fluorouracil (5-FU)-based adjuvant chemotherapy and 5-FU plasma concentrations in colorectal cancerpatients. METHODS: Thirty colorectal cancerpatients received adjuvant chemotherapy of leucovorin plus 5-FU after operations. The concentrations of UH(2), U and 5-FU were assayed by the high-performance liquid chromatography method. The relationships of the UH(2)/U ratios with the 5-FUtoxicities and 5-FU plasma concentrations were analyzed. RESULTS: There was a negative relationship between the UH(2)/U ratios and 5-FU plasma concentrations (p <0.001). 5-FUtoxicities had a negative correlation with the UH(2)/U ratios and a positive correlation with 5-FU plasma concentrations (p < 0.05). CONCLUSION: The UH(2)/U ratio in plasma has close correlations with the 5-FU plasma concentration and 5-FUtoxicity during chemotherapy, which may highlight the theoretical base of individual therapy for patients with colorectal cancer. Copyright 2007 S. Karger AG, Basel.
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