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: Drug monitoring; Feasibility; Fluorouracil; Pharmacokinetics.