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Fluorouracil is dosed by body size, yet the amount of drug in the blood varies widely between people given the same dose. Measuring the level during the infusion and adjusting the next dose raised the response rate from 18 to 34 per cent in one randomised trial and is recommended by an international pharmacology society, but it is not routine care and no survival gain has been established.
What it measures. Infusional fluorouracil is given in milligrams per square metre of body surface. A single blood sample taken while the infusion is running gives the drug's exposure as an area under the concentration-time curve, in milligram-hours per litre, and the next cycle's dose is raised or lowered towards a target range. A 2009 review in the Journal of the National Cancer Institute put the problem in one line: only 20 to 30 per cent of patients on a fluorouracil regimen dosed by surface area have blood levels in the therapeutic range, about 40 to 60 per cent are underdosed and 10 to 20 per cent overdosed. A model built on 589 patients receiving FOLFOX6 recommended adjusting every cycle to keep exposure between 20 and 30 milligram-hours per litre.
What the trials showed. The randomised trial, published in 2008, enrolled 208 people with metastatic colorectal cancer received weekly eight-hour infusions of fluorouracil with folinic acid, dosed either by surface area or by weekly blood levels aimed at 20 to 25 milligram-hours per litre. Response was 18.3 per cent with surface-area dosing and 33.7 per cent with level-guided dosing, median overall survival 16 and 22 months (a difference that did not reach statistical significance), and severe toxicity was commoner in the surface-area arm. The level-guided arm ended up with a higher mean dose, 1,790 against 1,500 milligrams per square metre a week, consistent with the review finding that underdosing is the commoner error. In 2019 the International Association of Therapeutic Drug Monitoring and Clinical Toxicology strongly recommended monitoring for colorectal and head and neck cancer on common fluorouracil regimens. A 2026 meta-analysis of five studies and 809 patients found level-guided dosing halved severe toxicity (risk ratio 0.50) and raised response (risk ratio 1.50), and said that progression-free and overall survival benefits could not be established from a small and heterogeneous evidence base.
Where it stands. Measuring exposure is precise; what that precision buys is shown for toxicity and response and not for survival. The randomised evidence used a weekly schedule rather than the FOLFOX and FOLFIRI regimens given today, and the observational evidence is mostly in metastatic colorectal cancer. The evidence is for infusional fluorouracil and says nothing about capecitabine, the tablet form. It is complementary to testing for DPD deficiency before the first dose, which finds the few people at risk of severe early toxicity; level-guided dosing corrects the commoner problem of too little drug.
A steady-state plasma fluorouracil concentration during a continuous infusion, multiplied by infusion time, estimates exposure; the next dose is changed in proportion to the gap between measured and target exposure.
Query for this technology: (TITLE:"Fluorouracil dosing by measured blood level" OR ABSTRACT:"Fluorouracil dosing by measured blood level" OR TITLE:"5-FU therapeutic drug monitoring" OR ABSTRACT:"5-FU therapeutic drug monitoring" OR TITLE:"5-FU AUC-guided dosing" OR ABSTRACT:"5-FU AUC-guided dosing" OR TITLE:"pharmacokinetically guided fluorouracil dosing" OR ABSTRACT:"pharmacokinetically guided fluorouracil dosing") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Fluorouracil dosing by measured blood level, not a curated reading list.
Shares Body-surface-area dosing, Pharmacokinetic and pharmacodynamic modelling, Pharmacokinetics (PK), half-life and exposure, Dose reduction, interruption and discontinuation and the tag precision.
Shares Body-surface-area dosing, Dose reduction, interruption and discontinuation, Wrong doses, Colorectal cancer and the tag precision.
Shares Pharmacokinetic and pharmacodynamic modelling, DPYD genotyping and DPD phenotyping before fluoropyrimidines, Fluorouracil (5-FU), Colorectal cancer and the tag precision.
Shares Pharmacokinetics (PK), half-life and exposure, DPYD genotyping and DPD phenotyping before fluoropyrimidines, Dose reduction, interruption and discontinuation and the tag precision.
Shares Pharmacokinetics (PK), half-life and exposure, DPYD genotyping and DPD phenotyping before fluoropyrimidines, Dose reduction, interruption and discontinuation, Colorectal cancer and the tag precision.
Shares Therapeutic index (therapeutic window), Pharmacokinetics (PK), half-life and exposure, Dose reduction, interruption and discontinuation and the tag precision.
Shares Body-surface-area dosing, Dose reduction, interruption and discontinuation, Head and neck squamous cell carcinoma, Colorectal cancer and the tag precision.
Shares DPYD genotyping and DPD phenotyping before fluoropyrimidines, Wrong doses, Fluorouracil (5-FU) and the tag precision.
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