This study investigated the relationship among the pharmacokinetics of 5-fluorouracil (5-FU) and 5-fluoro-5,6-dihydrouracil (5-FDHU); the activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells; and treatment-related toxicity in 26 patients with surgically resected colorectal cancer treated with short daily infusions of 5-FU adjuvant chemotherapy, each cycle consisting of 5 consecutive days every 4 weeks. After the first chemotherapeutic cycle, severe stomatitis and diarrhea occurred in 5 patients and were related to the variations in the systemic disposition of the drug rather than to DPD activity. These patients showed a significant decrease in 5-FU clearance, and an increase in the 5-FU/5-FDHU area under the time-concentration curve (AUC) ratio, as compared with patients who experienced mild toxicities, whereas a low DPD activity was observed in only 2 patients. In conclusion, the results of this study demonstrate that the alterations in 5-FU and 5-FDHU pharmacokinetics are related to severe toxicities in patients treated with short intravenous infusion of 5-FU.
|Autori:||DI PAOLO A; IBRAHIM T; DANESI R; MALTONI M; VANNOZZI F; FLAMINI E; ZOLI W; AMADORI D; DEL TACCA M|
|Titolo:||Relationship between plasma concentrations of 5-fluorouracil and 5-fluoro-5,6-dihydrouracil and toxicity of 5-fluorouracil infusions in cancer patients|
|Anno del prodotto:||2002|
|Digital Object Identifier (DOI):||10.1097/01.FTD.0000020645.40422.05|
|Appare nelle tipologie:||1.1 Articolo in rivista|