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Plasma 5-Fluorouracil Exposure, Clinical Outcomes, and Therapeutic Drug Monitoring in Advanced Colorectal Cancer
1
Department of Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
2
Department of Surgery, Tokyo Metropolitan Tobu Chiiki Hospital, Tokyo 125-8512, Japan
3
Misato Care Center, Aiyukai Medical Corporation, Misato, Saitama 341-0028, Japan
4
Molecular Medical Research Project, Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(10), 1673; https://doi.org/10.3390/cancers18101673
Submission received: 13 April 2026
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Revised: 7 May 2026
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Accepted: 18 May 2026
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Published: 21 May 2026
(This article belongs to the Special Issue Nutrition in Cancer Care: From Generalized to Personalized Adjunctive Therapy)
Simple Summary
Continuous-infusion 5-fluorouracil remains a key component of chemotherapy for colorectal cancer, but plasma drug exposure varies considerably among patients even when the dose is determined according to body surface area. This pilot study explored whether patient-level representative 5-fluorouracil exposure within the target AUC range was associated with tumor control, toxicity, and exploratory survival outcomes. Patients within the target range showed a lower frequency of clinically relevant adverse events and numerically favorable tumor control, whereas survival analyses were descriptive and hypothesis-generating. We also performed a preliminary method-comparison analysis of a prototype immunochromatographic assay for plasma 5-fluorouracil measurement. Although the assay showed a favorable correlation with the My-5FU assay, Bland–Altman analysis demonstrated relatively wide limits of agreement. These findings support the feasibility of further developing simplified therapeutic drug monitoring tools. Still, larger prospective validation studies are required before this prototype assay can guide clinical dose adjustment.
Abstract
Background/Objectives: Body-surface-area-based dosing of continuous-infusion 5-fluorouracil does not account for inter-individual pharmacokinetic variability. This pilot study explored whether patient-level representative plasma 5-fluorouracil exposure within the target area under the concentration–time curve (AUC) range was associated with clinical outcomes. It evaluated a prototype immunochromatographic assay as a preliminary monitoring tool. Methods: Fifteen patients with unresectable advanced or recurrent colorectal cancer who received continuous-infusion 5-fluorouracil-based chemotherapy were prospectively evaluated between 1 January 2017 and 30 April 2018. Plasma 5-fluorouracil levels were measured during eight treatment cycles at three time points in each cycle. Representative AUC values were calculated using median concentrations across cycles and interpreted as exploratory patient-level exposure indices. Tumor response, grade ≥2 adverse events, progression-free survival, and overall survival were assessed descriptively. Results: The median representative AUC was 24.3 mg·h/L. Eight patients (53.3%) were within the target range of 20–30 mg·h/L, whereas seven (46.7%) were outside it. Disease control was observed in 7 of 8 patients (87.5%) within the target range and in 3 of 7 patients (42.9%) outside it. Grade ≥2 adverse events were less frequent in the target-range group (2/8, 25.0%) than in the outside-range group (6/7, 85.7%; p = 0.041). Progression-free survival was numerically longer in the target-range group (17.2 vs. 9.2 months, p = 0.36), while overall survival did not differ clearly (p = 0.76); these survival analyses were exploratory. The prototype immunochromatographic assay showed a favorable correlation with the My-5FU assay (R2 = 0.762), but Bland–Altman analysis showed relatively wide limits of agreement. Conclusions: Target plasma 5-fluorouracil exposure was associated with lower clinically relevant toxicity and may support favorable tumor control in this pilot cohort. The prototype immunochromatographic method demonstrated preliminary feasibility for rapid plasma 5-FU monitoring but requires further validation before routine dose adjustment.
