A pharmacokinetic-based test to predict the risk of life-threatening 5-fluorouracil toxicities in cancer patients. G. Bocci, C. Barbara, F. Vannozzi, A. Di Paolo, A. Melosi, M. Battistoni, G. Barsanti, G. Allegrini, A. Falcone, M. Del Tacca; Department of Oncology, University of Pisa, Pisa, Italy; Division of Medical Oncology, General Hospital, Livorno, Italy; Division of Medical Oncology, General Hospital, Lucca, Italy Abstract: Background: The extensive use of 5-fluorouracil (5-FU) has attracted a great attention on dihydropyrimidine dehydrogenase (DPD), the enzyme responsible for detoxification of 5-FU to 5-fluoro-5,6-dihydrouracil (5-FDHU). The incidence of DPD deficiency is estimated to be around 3% and thus the related 5-FU life-threatening toxicity has significant clinical implications. Methods: In order to (1) investigate the clinical pharmacokinetics (PK) of 5-FU/5-FDHU in cancer patients administered with a 5-FU single low dose, (2) predict the systemic impairment of 5-FU catabolism and (3) prevent severe drug-related toxicity, 112 patients received 5-FU 250 mg/m2 as i.v. bolus before starting the planned 5-FU treatment (i.v. bolus of 370 mg/m2/day 5-FU for 5 days, or continuos infusion of 3800 mg/m2 5-FU for 48 h). HPLC analysis was performed on plasma (from 0 to 1.5 h after 5-FU) and peripheral blood mononuclear cell samples to calculate 5-FU/5-FDHU PK parameters and DPD activity, respectively. Adverse events were graded according to WHO scale. Results: The single 5-FU dose did not cause side effects in all tested patients. A significant correlation between 5-FU AUC and 5-FDHU AUC was found, whereas no correlations between DPD activity and 5-FU/5-FDHU PK were identified. Three patients had marked alterations of 5-FU/5-FDHU PK (e.g. 5-FU t1/2â>5 h; CLTB<1 L/h/m2; 5-FDHU Tmax>45 min) and were excluded from 5-FU treatments. After the first cycle of 5-FU-based therapy, only 4 of the 100 evaluated patients experienced a grade 3 toxicity. Conclusions: PK analysis of plasma 5-FU/5-FDHU after a test dose provides reliable information on the risk of developing toxicities due to impaired 5-FU catabolism and encourages its application to patients candidates to receive 5-FU chemotherapy (e.g. adjuvant treatment of colorectal cancer). Abstract No: 2052 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.