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Cancer Chemotherapy and Pharmacology

, Volume 82, Issue 5, pp 865–876 | Cite as

Feasibility of 5-fluorouracil pharmacokinetic monitoring using the My-5FU PCM™ system in a quaternary oncology centre

  • Michael Moloney
  • David Faulkner
  • Emma Link
  • Danny Rischin
  • Ben Solomon
  • Annette M. Lim
  • John R. Zalcberg
  • Michael Jefford
  • Michael Michael
Original Article
  • 50 Downloads

Abstract

Purpose

5-Fluorouracil (5FU) drug exposure correlates with treatment response and toxicity in cancer patients. Dosing is based upon body surface area which does not correlate with 5FU pharmacokinetics (PK)/pharmacodynamics. Therapeutic drug monitoring has enabled real-time 5FU dose adjustments: reducing toxicity with increased efficacy. The aim of this study was to assess feasibility of a 5FU monitoring service utilising a commercial kit in a quaternary cancer centre and to compare PK parameters to previously published studies.

Methods

Cancer patients receiving continuous infusional (CI) 5FU with ECOG PS 0–2, and adequate organ function, were eligible. Patients had blood samples taken at t = 0, mid infusion (if feasible) then 2 h pre infusion end. 5FU levels were measured using a commercial kit (My-5FU PCM™). A feasibility questionnaire was completed by trial nurses and toxicity data were recorded at baseline and at the commencement of the next cycle. 5FU pharmacokinetic exposure parameters were calculated.

Results

Twenty patients (12 male; 8 female), median age 62, (range 37–71) had samples taken. Twenty (100%) feasibility forms were available for assessment. Blood samples were taken at 51/69 (74%) specified time points. Ease of sample processing was recorded as easy in all 20 patients. Patient compliance with scheduled visits was 18/20 (90%). One form noted other difficulties with predicting end of infusion time. 19/20 patients had blood samples analysed. Mean measured 5FU AUC (0-Tlast) for 5FU 1 g/m2 with platinum: 35.8 h mg/L (range 28.56–44.26), mean Css 372.2 µg/L (range 297.5–461.0); 5FU 600 mg/m2 with platinum: 12.42 h mg/L (range 6.91–18.29), mean Css 111.0 µg/L (72.0–190.5) and 5FU 2400 mg/m2 as part of FOLFOX ± bevacizumab: 14.75 h mg/L (range 6.74–22.93), mean Css 320.70 µg/L (range 146.5–498.5). One patient had grade 4 neutropenia and one patient without PK parameters experienced febrile neutropenia (grade 4 neutropenia). Mucositis was observed in two patients: [5FU/platinum (1), grade 1, FOXFOX ± bevacizumab (1) grade 1]. Diarrhoea was reported in three patients [5FU/platinum (2) grade 1–2, FOXFOX ± bevacizumab (1) grade 1].

Conclusion

Therapeutic 5FU drug monitoring was feasible using commercial kits and analysers and hence warrants development as a routine standard of care in cancer patients. The variability in the 5FU exposure parameters is consistent with other studies using the My 5FU PCM kit.

Keywords

Fluorouracil Pharmacokinetics Drug monitoring Feasibility 

Notes

Compliance with ethical standards

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institution and the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Department of PathologyPeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.Centre of Biostatistics and Clinical TrialsPeter MacCallum Cancer CentreMelbourneAustralia
  4. 4.Department of Haematology and Medical OncologyPeter MacCallum Cancer CentreMelbourneAustralia
  5. 5.Sir Peter MacCallum Department of OncologyUniversity of MelbourneParkvilleAustralia
  6. 6.Department of Medical OncologySir Charles Gairdner HospitalNedlandsAustralia
  7. 7.Department of Epidemiology and Preventive Medicine School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia

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