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 2h pre infusion end. 5FU levels were measured using a commercial kit (My-5FU PCM (TM)). 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/m(2) with platinum: 35.8h mg/L (range 28.56-44.26), mean Css 372.2 mu g/L (range 297.5-461.0); 5FU 600 mg/m(2) with platinum: 12.42h mg/L (range 6.91-18.29), mean Css 111.0 mu g/L (72.0-190.5) and 5FU 2400 mg/m(2) as part of FOLFOX +/- bevacizumab: 14.75h mg/L (range 6.74-22.93), mean Css 320.70 mu g/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.