{"entity":{"id":"fluorouracil-pharmacokinetic-dosing","kind":"technology","name":"Fluorouracil dosing by measured blood level","aka":["5-FU therapeutic drug monitoring","5-FU AUC-guided dosing","pharmacokinetically guided fluorouracil dosing","PK-guided 5-FU dosing","fluorouracil TDM"],"tldr":"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.","summary":"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.\n\nWhat 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.\n\nWhere 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.","status":"emerging","asOf":"2026-10-20","links":[{"label":"Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer (J Clin Oncol 2008)","url":"https://doi.org/10.1200/JCO.2007.13.3934"},{"label":"Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5-Fluorouracil Therapy (Clin Pharmacol Ther 2019)","url":"https://doi.org/10.1002/cpt.1124"},{"label":"Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis (Eur J Clin Pharmacol 2026)","url":"https://doi.org/10.1007/s00228-026-04174-9"},{"label":"Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes (J Natl Cancer Inst 2009)","url":"https://doi.org/10.1093/jnci/djp328"},{"label":"Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6 (Oncologist 2012)","url":"https://doi.org/10.1634/theoncologist.2011-0357"}],"tags":["precision","evidence:moderate"],"related":[],"cancers":["colorectal","head-and-neck"],"sections":["chemotherapy","supportive-care"],"technologies":["body-surface-area-dosing","dpyd-genotyping","pkpd-modelling","oral-targeted-therapy-drug-monitoring"],"targets":[],"drugs":["fluorouracil"],"companies":[],"institutions":[],"pathways":[],"terms":["pharmacokinetics","therapeutic-index","dose-modification"],"trials":[],"people":[],"bottlenecks":["b-dose-optimisation"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"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.","strengths":["Addresses underdosing, which the review evidence says is commoner than overdosing","One randomised trial and a meta-analysis agree on lower toxicity and higher response","Recommended by the international therapeutic drug monitoring society"],"limitations":["No survival benefit established","The randomised trial used a weekly schedule no longer standard","Not widely used, which a 2009 review put down to the lack of a simple, fast and inexpensive assay"]},"route":"/technologies/fluorouracil-pharmacokinetic-dosing/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"technology":[{"id":"oral-targeted-therapy-drug-monitoring","kind":"technology","name":"Blood-level monitoring of oral targeted cancer drugs","route":"/technologies/oral-targeted-therapy-drug-monitoring/"},{"id":"body-surface-area-dosing","kind":"technology","name":"Body-surface-area dosing","route":"/technologies/body-surface-area-dosing/"},{"id":"dpyd-genotyping","kind":"technology","name":"DPYD genotyping and DPD phenotyping before fluoropyrimidines","route":"/technologies/dpyd-genotyping/"},{"id":"pkpd-modelling","kind":"technology","name":"Pharmacokinetic and pharmacodynamic modelling","route":"/technologies/pkpd-modelling/"}],"drug":[{"id":"fluorouracil","kind":"drug","name":"Fluorouracil (5-FU)","route":"/drugs/fluorouracil/"}],"term":[{"id":"dose-modification","kind":"term","name":"Dose reduction, interruption and discontinuation","route":"/terms/dose-modification/"},{"id":"pharmacokinetics","kind":"term","name":"Pharmacokinetics (PK), half-life and exposure","route":"/terms/pharmacokinetics/"},{"id":"therapeutic-index","kind":"term","name":"Therapeutic index (therapeutic window)","route":"/terms/therapeutic-index/"}],"bottleneck":[{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}]}}