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.
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Authors | Michael Moloney, David Faulkner, Emma Link, Danny Rischin, Ben Solomon, Annette M Lim, John R Zalcberg, Michael Jefford, Michael Michael |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 82
Issue 5
Pg. 865-876
(11 2018)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 30178115
(Publication Type: Journal Article, Observational Study)
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Chemical References |
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Topics |
- Aged
- Ambulatory Care
(methods)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, therapeutic use)
- Area Under Curve
- Blood Specimen Collection
- Drug Monitoring
(instrumentation, methods)
- Drug-Related Side Effects and Adverse Reactions
(blood, etiology, prevention & control)
- Feasibility Studies
- Female
- Fluorouracil
(administration & dosage, adverse effects, blood, therapeutic use)
- Humans
- Infusions, Intravenous
- Male
- Neoplasms
(blood, drug therapy)
- Oncology Service, Hospital
- Patient Compliance
- Pilot Projects
- Specimen Handling
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