Journal ArticleDOI
Overcoming barriers to implementing precision dosing with 5-fluorouracil and capecitabine
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TLDR
Issues and barriers to implementing precision dosing approaches for 5FU and capecitabine are identified and discussed with possible solutions proposed.Abstract:
Despite advances in targeted cancer therapy, the fluoropyrimidines 5-fluorouracil (5FU) and capecitabine continue to play an important role in oncology. Historically, dosing of these drugs has been based on body surface area. This approach has been demonstrated to be an imprecise way to determine the optimal dose for a patient. Evidence in the literature has demonstrated that precision dosing approaches, such as DPD enzyme activity testing and, in the case of intravenous 5FU, pharmacokinetic guided dosing, can reduce toxicity and yield better patient outcomes. However, despite the evidence, there has not been uniform adoption of these approaches in the clinical setting. When a drug such as 5FU has been used clinically for many decades, it may be difficult to change clinical practice. With the aim of facilitating change of practice, issues and barriers to implementing precision dosing approaches for 5FU and capecitabine are identified and discussed with possible solutions proposed.read more
Citations
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Journal ArticleDOI
Fluoropyrimidine chemotherapy: recommendations for DPYD genotyping and therapeutic drug monitoring of the Swiss Group of Pharmacogenomics and Personalised Therapy.
Seid Hamzic,Stefan Aebi,Markus Joerger,Michael Montemurro,Marc Ansari,Ursula Amstutz,Carlo R. Largiadèr +6 more
TL;DR: Current guidelines on genotype-guided FP dosing and TDM are discussed, and recommendations tailored to the situation in Switzerland are proposed to facilitate their clinical uptake for the further individualisation of FP chemotherapy.
Journal ArticleDOI
Measurement of 5- fluorouracil, capecitabine and its metabolite concentrations in blood using volumetric absorptive microsampling technology and LC-MS/MS
TL;DR: In this paper , a liquid chromatography mass spectrometry (LC-MS/MS) method for simultaneous measurement of capecitabine, 5-deoxy-5-fluorocytidine, 5'-deoxy5fluorouridine and 5-FU using Mitra® microsampling devices for sample collection was developed.
Journal ArticleDOI
Measurement of 5- fluorouracil, capecitabine and its metabolite concentrations in blood using volumetric absorptive microsampling technology and LC-MS/MS
Mirjana Radovanovic,Mirjana Radovanovic,Jennifer Schneider,Mohsen Shafiei,Jennifer H. Martin,Peter Galettis +5 more
TL;DR: In this paper, a liquid chromatography mass spectrometry (LC-MS/MS) method for simultaneous measurement of capecitabine, 5-deoxy-5-fluorocytidine, 5'deoxy5fluorouridine and 5-FU using Mitra® microsampling devices was developed.
Journal ArticleDOI
Precision medicine-based drug treatment individualization in oncology.
TL;DR: Discussion on the wide range of aspects of science and medicine referred to as ‘precision medicine approach’ are covered, including the importance of understanding the way each individual both handles and responds to a drug, including specific doses.
Journal ArticleDOI
Polymorphisms of MTHFR and TYMS to predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer.
TL;DR: Capecitabine, an oral prodrug of fluorouracil, has been reported to be effective in patients with breast cancer, and its use in clinical practice and animal studies has shown promising results.
References
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Journal ArticleDOI
Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients.
Johannes Schüller,Jim Cassidy,Etienne Dumont,Brigitte Roos,Sarah Durston,Ludger Banken,Masahiro Utoh,Kazushige Mori,Erhard Weidekamm,Bruno Reigner +9 more
TL;DR: Capecitabine is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil preferentially in tumors, which is explained to a great extent by the activity of TP in colorectal tumor tissue, (the enzyme responsible for the conversion of 5′-DFUR to 5-FU), which is approximately four times that in adjacent healthy tissue.
Journal ArticleDOI
Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity.
Carla M. Prado,Vickie E. Baracos,Linda J. McCargar,Marina Mourtzakis,Karen E. Mulder,Tony Reiman,Charles A. Butts,Andrew Scarfe,Michael B. Sawyer +8 more
TL;DR: Low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area, and it is concluded that variation in toxicity between females and males may be partially explained by this feature of body composition.
Journal ArticleDOI
Clinical Pharmacokinetics of Capecitabine
TL;DR: As with other cytotoxic drugs, the interpatient variability of the pharmacokinetic parameters of cape citabine and its metabolites, 5′-deoxy-5-fluorocytidine and fluorouracil, is high and is likely to be primarily due to variability in the activity of the enzymes involved in capecitabine metabolism.
Journal ArticleDOI
DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis.
Linda M. Henricks,Carin A.T.C. Lunenburg,Femke M. de Man,Didier Meulendijks,Geert W.J. Frederix,Emma Kienhuis,Geert Jan Creemers,Arnold Baars,Vincent O. Dezentjé,Alexander L T Imholz,Frank J.F. Jeurissen,Johanna E.A. Portielje,Rob L. H. Jansen,Paul Hamberg,Albert J. ten Tije,Helga J. Droogendijk,Miriam Koopman,Peter Nieboer,Marlène H.W. van de Poel,Caroline M.P.W. Mandigers,Hilde Rosing,Jos H. Beijnen,Jos H. Beijnen,Erik van Werkhoven,André B.P. van Kuilenburg,Ron H.N. van Schaik,Ron H.J. Mathijssen,Jesse J. Swen,Hans Gelderblom,Annemieke Cats,Henk-Jan Guchelaar,Jan H.M. Schellens,Jan H.M. Schellens +32 more
TL;DR: Overall, fluoropyrimidine-related severe toxicity was higher in DPYD variant carriers than in wild-type patients in this prospective, multicentre, safety analysis in 17 hospitals in the Netherlands, and relative risks for severe toxicity were compared between the current study and a historical cohort ofDPYD variant allele carriers treated with full dose fluoropyridine-based therapy.
Journal ArticleDOI
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
Erick Gamelin,Michèle Boisdron-Celle,Veronique Guerin-Meyer,Remy Delva,Alain Lortholary,F. Genevieve,F. Larra,Norbert Ifrah,Jacques Robert +8 more
TL;DR: The UH(2)-U ratio, easily determined before treatment, could help to identify patients with metabolic deficiency and, therefore, a risk of toxicity in patients treated for advanced colorectal cancer by high-dose 5-FU.