UNLABELLED: 5-Fluorouracil (5-FU)-related early toxicity, due to a metabolic deficiency, is rare but is potentially severe and even lethal (0.1%). It is due to dihydropyrimidine dehydrogenase (DPYD) gene polymorphism or some epigenetic factors. The detection of metabolic change could prevent severe toxicity, but until now it has not been carried out in clinical practice. PURPOSE: To find the simplest and most accurate pretherapeutic test to predict DPD deficiency in patients treated with 5-FU by comparing different approaches. RESULTS: Two hundred and fifty two French Caucasian patients treated by 5-FU infusion were studied. A two-step strategy, combining firstly SNP detection and uracil plasma measurement, followed, in cases where metabolic deficiency was suspected, by dihydrouracil/uracil ratio determination to confirm deficiency and to determine the optimum 5-FU dosage, appeared the best approach, with 83% and 82% sensitivity and specificity, respectively. CONCLUSION: These data support the future use of this approach, suitable to clinical practice, as screening test to identify DPD deficiency before 5-FU-based therapy.
UNLABELLED: 5-Fluorouracil (5-FU)-related early toxicity, due to a metabolic deficiency, is rare but is potentially severe and even lethal (0.1%). It is due to dihydropyrimidine dehydrogenase (DPYD) gene polymorphism or some epigenetic factors. The detection of metabolic change could prevent severe toxicity, but until now it has not been carried out in clinical practice. PURPOSE: To find the simplest and most accurate pretherapeutic test to predict DPD deficiency in patients treated with 5-FU by comparing different approaches. RESULTS: Two hundred and fifty two French Caucasian patients treated by 5-FU infusion were studied. A two-step strategy, combining firstly SNP detection and uracil plasma measurement, followed, in cases where metabolic deficiency was suspected, by dihydrouracil/uracil ratio determination to confirm deficiency and to determine the optimum 5-FU dosage, appeared the best approach, with 83% and 82% sensitivity and specificity, respectively. CONCLUSION: These data support the future use of this approach, suitable to clinical practice, as screening test to identify DPD deficiency before 5-FU-based therapy.
Authors: Bart A W Jacobs; Maarten J Deenen; Dick Pluim; J G Coen van Hasselt; Martin D Krähenbühl; Robin M J M van Geel; Niels de Vries; Hilde Rosing; Didier Meulendijks; Artur M Burylo; Annemieke Cats; Jos H Beijnen; Alwin D R Huitema; Jan H M Schellens Journal: Br J Clin Pharmacol Date: 2016-06-03 Impact factor: 4.335
Authors: Shyam Sundhar Bale; Gautham Vivek Sridharan; Inna Golberg; Ljupcho Prodanov; William J McCarty; Osman Berk Usta; Rohit Jindal; Martin L Yarmush Journal: Technology (Singap World Sci) Date: 2015-04-21
Authors: Bart A W Jacobs; Nikol Snoeren; Morsal Samim; Hilde Rosing; Niels de Vries; Maarten J Deenen; Jos H Beijnen; Jan H M Schellens; Miriam Koopman; Richard van Hillegersberg Journal: Eur J Clin Pharmacol Date: 2018-02-11 Impact factor: 2.953