Sites internationaux :

Publications scientifiques :

Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism. Berger R, Stoker-de Vries SA, Wadman SK, Duran M, Beemer FA, de Bree PK, Weits-Binnerts JJ, Penders TJ, van der Woude JK. Clin Chim Acta. 1984 Aug 31; 141(2-3):227-34.



Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. Diasio RB, Beavers TL, Carpenter JT. J Clin Invest. 1988 Jan; 81(1):47-51.



Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Harris BE, Carpenter JT, Diasio RB. Cancer. 1991 Aug 1; 68(3):499-501.



Dihydropyrimidine dehydrogenase activity in cancer patients. Fleming RA, Milano GA, Gaspard MH, Bargnoux PJ, Thyss A, Plagne R, Renée N, Schneider M, Demard F. Eur J Cancer. 1993; 29A(5):740-4.



Dihydropyrimidine dehydrogenase (DPD) and clinical pharmacology of 5-fluorouracil (review). Milano G, Etienne MC. Anticancer Res. 1994 Nov-Dec;14(6A):2295-7. Review.

Population study of dihydropyrimidine dehydrogenase in cancer patients. Etienne MC, Lagrange JL, Dassonville O, Fleming R, Thyss A, Renée N, Schneider M, Demard F, Milano G. J Clin Oncol. 1994 Nov; 12(11):2248-53.



Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. Meinsma R, Fernandez-Salguero P, Van Kuilenburg AB, Van Gennip AH, Gonzalez FJ. DNA Cell Biol. 1995 Jan; 14(1):1-6.

Population characteristics of hepatic dihydropyrimidine dehydrogenase activity, a key metabolic enzyme in 5-fluorouracil chemotherapy. Lu Z, Zhang R, Diasio RB. Clin Pharmacol Ther. 1995 Nov; 58(5):512-22



Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Takimoto CH, Lu ZH, Zhang R, Liang MD, Larson LV, Cantilena LR Jr, Grem JL, Allegra CJ, Diasio RB, Chu E. Clin Cancer Res. 1996 Mar; 2(3):477-81.

Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria. Hayashi K, Kidouchi K, Sumi S, Mizokami M, Orito E, Kumada K, Ueda R, Wada Y. Clin Cancer Res. 1996 Dec; 2(12):1937-41.



Dihydropyrimidine dehydrogenase deficiency: a pharmacogenetic defect causing severe adverse reactions to 5-fluorouracil-based chemotherapy. Morrison GB, Bastian A, Dela Rosa T, Diasio RB, Takimoto CH. Oncol Nurs Forum. 1997 Jan-Feb; 24(1):83-8. Review.



Decreased dihydropyrimidine dehydrogenase activity in a population of patients with breast cancer: implication for 5-fluorouracil-based chemotherapy. Lu Z, Zhang R, Carpenter JT, Diasio RB. Clin Cancer Res. 1998 Feb; 4(2):325-9.

Possible prediction of adverse reactions to fluorouracil by the measurement of urinary dihydrothymine and thymine. Sumi S, Kidouchi K, Kondou M, Hayashi K, Dobashi K, Kouwaki M, Togari H, Wada Y. Int J Mol Med. 1998 Oct;2(4):477-82.



Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. Gamelin E, Boisdron-Celle M, Guérin-Meyer V, Delva R, Lortholary A, Genevieve F, Larra F, Ifrah N, Robert J. J Clin Oncol. 1999 Apr; 17(4): 1105.

Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Van Kuilenburg AB, Vreken P, Abeling NG, Bakker HD, Meinsma R, Van Lenthe H, De Abreu RA, Smeitink JA, Kayserili H, Apak MY, Christensen E, Holopainen I, Pulkki K, Riva D, Botteon G, Holme E, Tulinius M, Kleijer WJ, Beemer FA, Duran M, Niezen-Koning KE, Smit GP, Jakobs C, Smit LM, Van Gennip AH, et al. Hum Genet. 1999 Jan; 104(1):1-9. Review.

Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB. Clin Cancer Res. 1999 Aug; 5(8):2006-11.



Rapid screening of high-risk patients for disorders of purine and pyrimidine metabolism using HPLC-electrospray tandem mass spectrometry of liquid urine or urine-soaked filter paper strips. Ito T, van Kuilenburg AB, Bootsma AH, Haasnoot AJ, van Cruchten A, Wada Y, van Gennip AH. Clin Chem. 2000 Apr;46(4):445-52.



Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5-fluorouracil: frequency of the common IVS14+1G>A mutation causing DPD deficiency. van Kuilenburg AB, Muller EW, Haasjes J, Meinsma R, Zoetekouw L, Waterham HR, Baas F, Richel DJ, van Gennip AH. Clin Cancer Res. 2001 May; 7(5):1149-53.

Detection of beta-ureidopropionase deficiency with HPLC-electrospray tandem mass spectrometry and confirmation of the defect at the enzyme level. Van Kuilenburg AB, Van Lenthe H, Assmann B, Göhlich-Ratmann G, Hoffmann GF, Bräutigam C, Wevers RA, Van Gennip AH. J Inherit Metab Dis. 2001 Dec; 24(7):725-32.



Diagnosis of dihydropyrimidine dehydrogenase deficiency in a neonate with thymine-uraciluria. Au KM, Lai CK, Yuen YP, Shek CC, Lam CW, Chan AY. Hong Kong Med J. 2003 Apr; 9(2):130-2.

Rapid gas chromatographic-mass spectrometric diagnosis of dihydropyrimidine dehydrogenase deficiency and dihydropyrimidinase deficiency. Kuhara T, Ohdoi C, Ohse M, van Kuilenburg AB, van Gennip AH, Sumi S, Ito T, Wada Y, Matsumoto I. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):107-15.



Rapid identification of dihydropyrimidine dehydrogenase deficiency by using a novel 2-13C-uracil breath test. Mattison LK, Ezzeldin H, Carpenter M, Modak A, Johnson MR, Diasio RB. Clin Cancer Res. 2004 Apr 15; 10(8):2652-8.

Dihydropyrimidine dehydrogenase deficiency, a pharmacogenetic syndrome associated with potentially life-threatening toxicity following 5-fluorouracil administration. Ezzeldin H, Diasio R. Clin Colorectal Cancer. 2004 Sep; 4(3):181-9. Review.

Important role of the dihydrouracil/uracil ratio in marked interpatient variations of fluoropyrimidine pharmacokinetics and pharmacodynamics. Jiang H, Lu J, Jiang J, Hu P. J Clin Pharmacol. 2004 Nov; 44(11):1260-72.



An accurate dihydrouracil/uracil determination using improved high performance liquid chromatography method for preventing fluoropyrimidines-related toxicity in clinical practice. Remaud G, Boisdron-Celle M, Hameline C, Morel A, Gamelin E. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 5;823(2):98-107



Toxic death-case after capecitabine + oxaliplatin (XELOX) administration: probable implication of dihydropyrimidine deshydrogenase deficiency. Ciccolini J, Mercier C, Dahan L, Evrard A, Boyer JC, Richard K, Dales JP, Durand A, Milano G, Seitz JF, Lacarelle B. Cancer Chemother Pharmacol. 2006 Aug; 58(2):272-5

The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]dihydrouracil. Mattison LK, Fourie J, Hirao Y, Koga T, Desmond RA, King JR, Shimizu T, Diasio RB. Clin Cancer Res. 2006 Jan 15; 12(2):549-55

A rapid and inexpensive method for anticipating severe toxicity to fluorouracil and fluorouracil-based chemotherapy. Ciccolini J, Mercier C, Evrard A, Dahan L, Boyer JC, Duffaud F, Richard K, Blanquicett C, Milano G, Blesius A, Durand A, Seitz JF, Favre R, Lacarelle B. Ther Drug Monit. 2006 Oct; 28(5):678-85.

Increased prevalence of dihydropyrimidine dehydrogenase deficiency in African-Americans compared with Caucasians. Mattison LK, Fourie J, Desmond RA, Modak A, Saif MW, Diasio RB. Clin Cancer Res. 2006 Sep 15; 12(18):5491-5.

Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Morel A, Boisdron-Celle M, Fey L, Soulie P, Craipeau MC, Traore S, Gamelin E. Mol Cancer Ther. 2006 Nov; 5(11):2895-904.



5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Boisdron-Celle M, Remaud G, Traore S, Poirier AL, Gamelin L, Morel A, Gamelin E. Cancer Lett. 2007 May 8;249(2):271-82

HPLC-electrospray tandem mass spectrometry for rapid determination of dihydropyrimidine dehydrogenase activity. van Kuilenburg AB, van Lenthe H, Zoetekouw L, Kulik W. Clin Chem. 2007 Mar;53(3):528-30.

Should DPD analysis be required prior to prescribing fluoropyrimidines? Yen JL, McLeod HL. Eur J Cancer. 2007 Apr;43(6):1011-6

Detection of dihydropyrimidine dehydrogenase deficiency before treatment by fluoropyrimidines. Gamelin E, Boisdron-Celle M, Morel A. Therapie. 2007 Mar-Apr; 62(2):99-103

Pharmacogenetics of anti-cancer drugs. Gamelin E, Boisdron-Celle M, Morel A, Capitain O. Ann Pharm Fr. 2007 Nov; 65(6):390-401



A well-tolerated 5-FU-based treatment subsequent to severe capecitabine-induced toxicity in a DPD-deficient patient. Blasco H, Boisdron-Celle M, Bougnoux P, Calais G, Tournamille JF, Ciccolini J, Autret-Leca E, Le Guellec C. Br J Clin Pharmacol. 2008 Jun;65(6):966-70

Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy. Grau JJ, Caballero M, Monzó M, Muñoz-García C, Domingo-Domenech J, Navarro A, Conill C, Campayo M, Bombí JA. J Surg Oncol. 2008 Aug 1; 98(2):130-4



The dihydrouracil/uracil ratio in plasma, clinical and genetic analysis for screening of dihydropyrimidine dehydrogenase deficiency in colorectal cancer patients treated with 5-fluorouracil. Ben Fredj R, Gross E, Ben Ahmed S, Hassine H, Saguem S. Pathol Biol (Paris). 2009 Sep; 57(6):470-6



Prerequisites to the administration and prevention of adverse effects of chemotherapy in colorectal cancer. Bouché O, Scaglia E, Lagarde S. Bull Cancer. 2010 Feb; 97(2):265-80

Severe bone marrow suppression during adjuvant chemotherapy for gastric cancer by S-1 and its possible relationship to dihydropyrimidine dehydrogenase deficiency. Aragane H, Suchi K, Shimomura M, Katano T, Yasui H, Kan K. Gan To Kagaku Ryoho. 2010 Jan; 37(1):131-3

Dihydropyrimidine dehydrogenase deficiency and toxicity to fluoropyrimidine. Boisdron-Celle M, Morel A, Gamelin E. Ann Biol Clin (Paris). 2010 Jan-Feb; 68(1):27-32

Niveau de preuve du suivi thérapeutique pharmacologique du 5-fluorouracile au décours de son administration dans le traitement des cancers des voies aérodigestives supérieures et du cancer colorectal. Boisdron-Celle M, Le Guellec C; pour le groupe Suivi Thérapeutique Pharmacologique de la Société Française de Pharmacologie et de Thérapeutique. Therapie. 2010 May-Jun;65(3):171-6

Severe toxicity following capecitabine administration because of dihydropyrimidine deshydrogenase (DPD) deficiency. Coursier S, Martelet S, Guillermet A, Emptoz J, Villier C, Bontemps H. Gastroenterol Clin Biol. 2010 Mar;34(3):218-23

Lethal outcome of 5-fluorouracil infusion in a patient with a total DPD deficiency and a double DPYD and UTG1A1 gene mutation. Mounier-Boutoille H, Boisdron-Celle M, Cauchin E, Galmiche JP, Morel A, Gamelin E, Matysiak-Budnik T. Br J Clin Pharmacol. 2010 Aug; 70(2):280-3

Routine dihydropyrimidine dehydrogenase testing for anticipating 5-fluorouracil-related severe toxicities: hype or hope? Ciccolini J, Gross E, Dahan L, Lacarelle B, Mercier C. Clin Colorectal Cancer. 2010 Oct; 9(4):224-8

The value of dihydrouracil/uracil plasma ratios in predicting 5-fluorouracil-related toxicity in colorectal cancer patients. Kristensen MH, Pedersen P, Mejer J. J Int Med Res. 2010 Jul-Aug; 38(4)



Prevention of severe toxicity from capecitabine, 5-fluorouracil and tegafur by screening for DPD-deficiency. Deenen MJ, Cats A, Mandigers CM, Soesan M, Terpstra WE, Beijnen JH, Schellens JH. Ned Tijdschr Geneeskd. 2012; 156(48)



Dihydropyrimidine dehydrogenase gene (DPYD) polymorphism among Caucasian and non-Caucasian patients with 5-FU- and capecitabine-related toxicity using full sequencing of DPYD. Saif MW. Cancer Genomics Proteomics. 2013 Mar-Apr; 10(2):89-92.

Actualités en Pharmacovigilance: 5-Fluorouracile et capécitabine: éviter les toxicités potentiellement mortelles.”Le dépistage prèthérapeutique du déficit en DPD doit devenir une nécessité…” Edition n°50 d’avril 2013 du Bulletin d’information du Centre Régional de Pharmacovigilance d’Angers

5-fluorouracile: MSI, phamacocinétique, DPD, TYMS et MTHFR. Boisdron-Celle M, Guérin-Meyer V, Capitain O. Chapitre 6 du livre «Médecine Personnalisée en Cancérologie Digestive, vers un traitement à la carte» édition 2013 Springer

A case of good response in a rectal cancer patient with decreased dihydropyrimidine dehydrogenase activity because of strict control of the 5-fluorouracil dose. Tsukiyama G, Hasegawa M, Yabuki S, Tanaka H, Tanahashi C. Gan To Kagaku Ryoho. 2013 Nov; 40(12):2023-5

Dihydropyrimidine dehydrogenase and fluoropyrimidines: a review of current dose adaptation practices and the impact on the future of personalized medicine using 5-fluorouracile. Boisdron-Celle M, Biason P, Gamelin E et al. Colorectal Cancer 2(6), 1-11 (2013)



Development and validation of a rapid and sensitive UPLC-MS/MS method for determination of uracil and dihydrouracil in human plasma. Jacobs BA, Rosing H, de Vries N, Meulendijks D, Henricks LM, Schellens JH, Beijnen JH. J Pharm Biomed Anal. 2016 Jul 15; 126:75-82

Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency. Saif MW, Diasio RB. Cancer Chemother Pharmacol. 2016 Jul; 78(1):151-6

Improving safety of fluoropyrimidine chemotherapy by individualizing treatment based on dihydropyrimidine dehydrogenase activity – Ready for clinical practice? Meulendijks D, Cats A, Beijnen JH, Schellens JH. Cancer Treat Rev. 2016 Nov; 50:23-34

Endogenous plasma and salivary uracil to dihydrouracil ratios and DPYD genotyping as predictors of severe fluoropyrimidine toxicity in patients with gastrointestinal malignancies. Galarza AF, Linden R, Antunes MV, Hahn RZ, Raymundo S, da Silva AC, Staggemeier R, Spilki FR, Schwartsmann G. Clin Biochem. 2016 Nov; 49(16-17):1221-1226



Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity. Ma WW, Saif MW, El-Rayes BF, Fakih MG, Cartwright TH, Posey JA, King TR, von Borstel RW, Bamat MK. Cancer. 2017 Jan 1; 123(2):345-356

Recommendation on testing for dihydropyrimidine dehydrogenase deficiency in the ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Deenen MJ, Meulendijks D. Ann Oncol. 2017 Jan 1; 28(1):184

Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach. Boisdron-Celle M, Capitain O, Faroux R, Borg C, Metges JP, Galais MP, Kaassis M, Bennouna J, Bouhier-Leporrier K, Francois E, Baumgaertner I, Guerin-Meyer V, Cojocarasu O, Roemer-Becuwe C, Stampfli C, Rosenfeld L, Lecompte T, Berger V, Morel A, Gamelin E. Semin Oncol. 2017 Feb;44(1):13-23

Suivi thérapeutique du 5-fluorouracile (5-FU). EMC – Biologie médicale 1 Volume 12, n◦2, avril 2017. M. Boisdron-Celle, E. Gamelin, A. Morel