Thymine as potential biomarker to predict 5-FU systemic exposure in patients with gastro-intestinal cancer: a prospective pharmacokinetic study (FUUT-trial)

Tsalic M, Bar-Sela G, Beny A, Visel B, Haim N (2003) Severe toxicity related to the 5-fluorouracil/leucovorin combination (The Mayo Clinic Regimen). Am J Clin Oncol 26:103–106. https://doi.org/10.1097/01.COC.0000017526.55135.6D

Article  CAS  PubMed  Google Scholar 

Meta-Analysis Group In Cancer, Lévy E, Piedbois P, Buyse M, Pignon JP, Rougier P, et al (1998) Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 16:3537–41. https://doi.org/10.1200/JCO.1998.16.11.3537.

Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M et al (2001) Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19:2282–2292. https://doi.org/10.1200/JCO.2001.19.8.2282

Article  CAS  PubMed  Google Scholar 

Etienne MC, Lagrange JL, Dassonville O, Fleming R, Thyss A, Renée N et al (1994) Population study of dihydropyrimidine dehydrogenase in cancer patients. J Clin Oncol 12:2248–2253. https://doi.org/10.1200/JCO.1994.12.11.2248

Article  CAS  PubMed  Google Scholar 

Lu Z, Zhang R, Diasio RB (1993) Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res 53:5433–5438

CAS  PubMed  Google Scholar 

Diasio RB, Beavers TL, Carpenter JT (1988) Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Invest 81:47–51. https://doi.org/10.1172/JCI113308

Fleming RA, Milano G, Thyss A, Etienne MC, Renée N, Schneider M et al (1992) Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients. Cancer Res 52:2899–2902

CAS  PubMed  Google Scholar 

Meulendijks D, Henricks LM, Sonke GS, Deenen MJ, Froehlich TK, Amstutz U, et al (2015) Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data. Lancet Oncol 16:1639–50. https://doi.org/10.1016/S1470-2045(15)00286-7

Henricks LM, Lunenburg CATC, de Man FM, Meulendijks D, Frederix GWJ, Kienhuis E et al (2018) DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19:1459–1467. https://doi.org/10.1016/S1470-2045(18)30686-7

Article  CAS  PubMed  Google Scholar 

Deenen MJ, Meulendijks D, Cats A, Sechterberger MK, Severens JL, Boot H et al (2016) Upfront genotyping of DPYD * 2A to individualize fluoropyrimidine therapy: a safety and cost analysis. J Clin Oncol 34:227–234. https://doi.org/10.1200/JCO.2015.63.1325

Article  CAS  PubMed  Google Scholar 

European Medicines Agency (EMA) (2020) EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine

de With M, Sadlon A, Cecchin E, Haufroid V, Thomas F, Joerger M et al (2023) Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe. ESMO Open 8:101197. https://doi.org/10.1016/j.esmoop.2023.101197

Article  PubMed  PubMed Central  Google Scholar 

Meulendijks D, Cats A, Beijnen JH, Schellens JHM (2016) Improving safety of fluoropyrimidine chemotherapy by individualizing treatment based on dihydropyrimidine dehydrogenase activity – Ready for clinical practice? Cancer Treat Rev 50:23–34. https://doi.org/10.1016/j.ctrv.2016.08.002

Article  CAS  PubMed  Google Scholar 

Meulendijks D, Henricks LM, Jacobs BAW, Aliev A, Deenen MJ, de Vries N et al (2017) Pretreatment serum uracil concentration as a predictor of severe and fatal fluoropyrimidine-associated toxicity. Br J Cancer 116:1415–1424. https://doi.org/10.1038/bjc.2017.94

Article  CAS  PubMed  PubMed Central  Google Scholar 

Beumer JH, Chu E, Allegra C, Tanigawara Y, Milano G, Diasio R et al (2019) Therapeutic drug monitoring in oncology: international association of therapeutic drug monitoring and clinical toxicology recommendations for 5-fluorouracil therapy. Clin Pharmacol Ther 105:598–613. https://doi.org/10.1002/cpt.1124

Article  PubMed  Google Scholar 

Maring JG, van Kuilenburg ABP, Haasjes J, Piersma H, Groen HJM, Uges DRA et al (2002) Reduced 5-FU clearance in a patient with low DPD activity due to heterozygosity for a mutant allele of the DPYD gene. Br J Cancer 86:1028–1033. https://doi.org/10.1038/sj.bjc.6600208

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Kuilenburg ABP, Häusler P, Schalhorn A, Tanck MWT, Proost JH, Terborg C, et al (2012) Evaluation of 5-fluorouracil pharmacokinetics in cancer patients with a C.1905+1G>A mutation in DPYD by means of a Bayesian Limited Sampling Strategy. Clin Pharmacokinet 51:163–74. https://doi.org/10.1007/BF03257473

Li M, Mindt S, Lück A, Hutzschenreuter U, Kollendt M, Lathan B et al (2023) Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy—results of a prospective, multicenter German observational study. ESMO Open 8:101201. https://doi.org/10.1016/j.esmoop.2023.101201

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gamelin EC, Danquechin-Dorval EM, Dumesnil YF, Maillart PJ, Goudier MJ, Burtin PC et al (1996) Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU. Cancer 77:441–451. https://doi.org/10.1002/(SICI)1097-0142(19960201)77:3%3c441::AID-CNCR4%3e3.0.CO;2-N

Article  CAS  PubMed  Google Scholar 

Gamelin E, Boisdron-Celle M, Guérin-Meyer V, Delva R, Lortholary A, Genevieve F et al (1999) 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. J Clin Oncol 17:1105–1105. https://doi.org/10.1200/JCO.1999.17.4.1105

Article  CAS  PubMed  Google Scholar 

van den Wildenberg SAH, Streng AS, van den Broek R, Broeren MAC, Deenen MJ, van Dongen JLJ et al (2022) Quantification of uracil, dihydrouracil, thymine and dihydrothymine for reliable dihydropyrimidine dehydrogenase (DPD) phenotyping critically depend on blood and plasma storage conditions. J Pharm Biomed Anal 221:115027. https://doi.org/10.1016/j.jpba.2022.115027

Article  CAS  PubMed  Google Scholar 

Zhou ZW, Wang GQ, Wan D Sen, Lu ZH, Chen YB, Li S, et al (2007) The dihydrouracil/uracil ratios in plasma and toxicities of 5-fluorouracil-based adjuvant chemotherapy in colorectal cancer patients. Chemotherapy 53:127–31. https://doi.org/10.1159/000099984

Cunha-Junior GF, De Marco L, Bastos-Rodrigues L, Bolina MB, Martins FL, Pianetti GA et al (2013) 13C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients. Cancer Chemother Pharmacol 72:1273–1282. https://doi.org/10.1007/s00280-013-2309-4

Article  CAS  PubMed  Google Scholar 

Heersche N, Knikman JE, De With M, Lopez-Yurda M, Baars A, Creemers G-J et al (2024) 596P Dose-individualisation of fluoropyrimidines in DPYD wild-type patients: Final results from the Alpe2U study. Ann Oncol 35:S478–S479. https://doi.org/10.1016/j.annonc.2024.08.665

Article  Google Scholar 

Knikman J, de With M, Heersche N, Lopez-Yurda, Baars A, Creemers G, et al (n.d.) Dose-individualisation of fluoropyrimidines based on pre-treatment serum uracil levels: a safety and pharmacokinetic analysis from the Alpe2U study

Etienne-Grimaldi M-C, Boyer J-C, Beroud C, Mbatchi L, van Kuilenburg A, Bobin-Dubigeon C et al (2017) New advances in DPYD genotype and risk of severe toxicity under capecitabine. PLoS ONE 12:e0175998. https://doi.org/10.1371/journal.pone.0175998

Article  CAS  PubMed  PubMed Central  Google Scholar 

de With M, Knikman J, de Man FM, Lunenburg CATC, Henricks LM, van Kuilenburg ABP et al (2022) Dihydropyrimidine dehydrogenase phenotyping using pretreatment uracil: a note of caution based on a large prospective clinical study. Clin Pharmacol Ther 112:62–68. https://doi.org/10.1002/cpt.2608

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tybirk L, Hoffmann-Lücke E, Greibe E (2023) Instability of uracil in whole blood might affect cancer treatment with fluoropyrimidines. Clin Chim Acta 538:87–90. https://doi.org/10.1016/j.cca.2022.10.017

Article  CAS  PubMed  Google Scholar 

Jacobs BAW, Deenen MJ, Pluim D, van Hasselt JGC, Krähenbühl MD, van Geel RMJM et al (2016) Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers. Br J Clin Pharmacol 82:706–716. https://doi.org/10.1111/bcp.13007

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jacobs BAW, Snoeren N, Samim M, Rosing H, de Vries N, Deenen MJ et al (2018) The impact of liver resection on the dihydrouracil:uracil plasma ratio in patients with colorectal liver metastases. Eur J Clin Pharmacol 74:737–744. https://doi.org/10.1007/s00228-018-2426-4

Article  CAS  PubMed  Google Scholar 

Henricks LM, Jacobs BAW, Meulendijks D, Pluim D, van den Broek D, de Vries N et al (2018) Food-effect study on uracil and dihydrouracil plasma levels as marker for dihydropyrimidine dehydrogenase activity in human volunteers. Br J Clin Pharmacol 84:2761–2769. https://doi.org/10.1111/bcp.13719

Article  CAS  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif