Therapeutic drug monitoring (TDM) of 5-fluorouracil (5-FU): new preanalytic aspects.
5-fluorouracil
colorectal carcinoma
preanalytic
therapeutic drug monitoring
Journal
Clinical chemistry and laboratory medicine
ISSN: 1437-4331
Titre abrégé: Clin Chem Lab Med
Pays: Germany
ID NLM: 9806306
Informations de publication
Date de publication:
26 06 2019
26 06 2019
Historique:
received:
02
11
2018
accepted:
16
12
2018
pubmed:
31
1
2019
medline:
26
2
2020
entrez:
31
1
2019
Statut:
ppublish
Résumé
Background 5-Fluorouracil (5-FU) is frequently used for the treatment of gastrointestinal tumors. The pharmacological effect of 5-FU is influenced by genetic polymorphisms as well as differently dosed regimens. Currently, 5-FU is generally administered as a continuous infusion via an implanted port system using a body surface area (BSA)-based dose calculation. In order to optimize treatment, the area under the curve (AUC) can be estimated to allow for individual dose adjustment. A 5-FU AUC range between 20 and 30 [mg×h×L] is recommended. The aim of the current study was to assess if blood for AUC analysis could also be drawn at the side where the port system had been placed. Methods We collected EDTA blood samples of patients receiving infusional 5-FU simultaneously from different sampling points (right/left cubital vein). 5-FU concentrations were measured in a steady-state equilibrium based on nanoparticle immunoassay (My5-FU; Saladax). Results A total of 39 patients took part in this study. About half of the patients did not reach the target 5-FU concentration window (37% were under- and 16% of the patients were overdosed). Calculated median AUC was 23.3 for the right arm (range 5.8-59.4) and a median of 23.4 for the left arm (range 5.3-61.0). AUC values showed no difference between right compared to left arms (p=0.99). Conclusions In all, these results confirm that a high percentage of patients are not treated with 5-FU doses reaching suggested AUC levels of 20-30. The location of venepuncture, however, had no impact on the results of plasma 5-FU concentration.
Identifiants
pubmed: 30699067
doi: 10.1515/cclm-2018-1177
pii: cclm-2018-1177
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1012-1016Références
Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005;352:476–87.
Goldberg RM. Which strategies will lead to progress in the management of colorectal cancer? Gastrointest Caner Res 2007; 1(4 Suppl 2):S33–6.
Fety R, Rolland F, Barberi-Heyob M, Hardouin A, Campion L, Conroy T, et al. Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas. Clin Cancer Res 1998;4:2039–45.
Baker SD, Verweij J, Rowinsky EK, Donehower RC, Schellens JH, Grochow LB, et al. Role of body surface area in dosing of investigational anticancer agents in adults, 1991–2001. J Natl Cancer Inst 2002;94:1883–8.
Undevia SD, Gomez-Abuin G, Ratain MJ. Pharmacokinetic variability of anticancer agents. Nat Rev Cancer 2005;5:447–58.
Hon YY, Evans WE. Making TDM work to optimize cancer chemotherapy: a multidisciplinary team approach. Clin Chem 1998;44:388–400.
McDonald GB, Slattery JT, Bouvier ME, Ren S, Batchelder AL, Kalhorn TF, et al. Cyclophosphamide metabolism, liver toxicity, and mortality following hematopoietic stem cell transplantation. Blood 2003;101:2043–8.
de Jonge ME, Huitema AD, Schellens JH, Rodenhuis S, Beijnen JH. Individualised cancer chemotherapy: strategies and performance of prospective studies on therapeutic drug monitoring with dose adaptation: a review. Clin Pharmacokinet 2005;44:147–73.
Gamelin E, Boisdron-Celle M, Guerin-Meyer V, Delva R, Lortholary A, Genevieve F, et al. 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 1999;17:1105.
Milano G, Etienne MC, Cassuto-Viguier E, Thyss A, Santini J, Frenay M, et al. Influence of sex and age on fluorouracil clearance. J Clin Oncol 1992;10:1171–5.
Beumer JH, Chu E, Allegra C, Tanigawara Y, Milano G, Diasio R, et al. Therapeutic drug monitoring in oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology recommendations for 5-fluorouracil therapy. Clin Pharmacol Ther 2018. doi: 10.1002/cpt.1124.
Kaldate RR, Haregewoin A, Grier CE, Hamilton SA, McLeod HL. Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6. Oncologist 2012;17:296–302.
Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, et al. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer. J Clin Oncol 2008;26:2099–105.
Capitain O, Asevoaia A, Boisdron-Celle M, Poirier AL, Morel A, Gamelin E. Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study. Clin Colorectal Cancer 2012;11:263–7.
Freeman K, Saunders MP, Uthman OA, Taylor-Phillips S, Connock M, Court R, et al. Is monitoring of plasma 5-fluorouracil levels in metastatic/advanced colorectal cancer clinically effective? A systematic review. BMC Cancer 2016;16:523.
Beumer JH, Boisdron-Celle M, Clarke W, Courtney JB, Egorin MJ, Gamelin E, et al. Multicenter evaluation of a novel nanoparticle immunoassay for 5-fluorouracil on the Olympus AU400 analyzer. Ther Drug Monit 2009;31:688–94.
Wilhelm M, Mueller L, Miller MC, Link K, Holdenrieder S, Bertsch T, et al. Prospective, multicenter study of 5-fluorouracil therapeutic drug monitoring in metastatic colorectal cancer treated in routine clinical practice. Clin Colorectal Cancer 2016;15:381–8.