Multicenter Evaluation of a Novel Nanoparticle Immunoassay for 5-Fluorouracil on the Olympus AU400 Analyzer

Beumer, Jan H.; Boisdron‐Celle, Michèle; Clarke, William; Courtney, Jodi B.; Egorin, Merrill J.; Gamelin, Érick; Harney, Rebecca L.; Hammett‐Stabler, Catherine A.; Lepp, Sandy; Li, Yunying; Lundell, G. D.; McMillin, Gwen A; Milano, Gérard; Salamone, Salvatore J.

doi:10.1097/ftd.0b013e3181b9b8c0

Cited by 45 publications

(35 citation statements)

References 21 publications

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“…95 The risk of bias was difficult to judge due to incomplete reporting, particularly in the domain of flow and timing. There was a high risk of bias for patient selection for two out of the four studies, 89,95 and it was unclear for the other two (S. Salamone, personal communication). 129 This was because there were no assurances given that inappropriate exclusions of patients or samples were made.…”

Section: Identificationmentioning

confidence: 99%

“…Two research papers 89,95 and two abstracts, 128,129 were found to include information relevant to whether or not My5-FU can be considered equivalent to LC-MS/MS and HPLC. However, one of the abstracts was considered part of the same study as one of the papers.…”

Section: Identificationmentioning

confidence: 99%

“…Beumer et al 89 describe part of the development and testing of the My5-FU assay with the corresponding author (a Saladax employee). They used 156 plasma samples from the blood of 156 H&N cancer and CRC patients.…”

Section: Identificationmentioning

confidence: 99%

“…Outlier results > 50 mg × hour/l are assumed to indicate that the blood sample has been taken too close to the infusion port and these results are disregarded. The My5-FU assay has been validated against liquid chromatography-mass spectrometry (LC-MS) 89,95 and high-performance liquid chromatography (HPLC) laboratory techniques commonly used in PK studies.…”

Section: My5-fu Assaymentioning

confidence: 99%

“…In short, photometric detection (changes in absorbance) of nanoparticle aggregation allows for determination of 5-FU concentration in plasma samples. 89 This assay can be performed on automated clinical chemistry analysers present in standard clinical laboratories. The assay requires a peripheral venous blood sample which is taken towards the end of each 5-FU infusion cycle using an ethylenediaminetetraacetic acid (EDTA) or a heparin tube.…”

Section: My5-fu Assaymentioning

confidence: 99%

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Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion

Freeman

Connock

Cummins³

et al. 2015

Health Technol Assess

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Background5-Fluorouracil (5-FU) is a chemotherapy used in colorectal, head and neck (H&N) and other cancers. Dose adjustment is based on body surface area (BSA) but wide variations occur. Pharmacokinetic (PK) dosing is suggested to bring plasma levels into the therapeutic range to promote fewer side effects and better patient outcomes. We investigated the clinical effectiveness and cost-effectiveness of the My5-FU assay for PK dose adjustment to 5-FU therapy.ObjectivesTo systematically review the evidence on the accuracy of the My5-FU assay compared with gold standard methods [high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS)]; the effectiveness of My5-FU PK dosing compared with BSA; the effectiveness of HPLC and/or LC-MS compared with BSA; the generalisability of published My5-FU and PK studies; costs of using My5-FU; to develop a cost-effectiveness model.Data sourcesWe searched MEDLINE, EMBASE, Science Citation Index and other databases between January and April 2014.MethodsTwo reviewers independently screened titles and abstracts with arbitration and consensus agreement. We undertook quality assessment. We reconstructed Kaplan–Meier plots for progression-free survival (PFS) and overall survival (OS) for comparison of BSA and PK dosing. We developed a Markov model to compare My5-FU with BSA dosing which modelled PFS, OS and adverse events, using a 2-week cycle over a 20 year time horizon with a 3.5% discount rate. Health impacts were evaluated from the patient perspective, while costs were evaluated from the NHS and Personal Social Services perspective.ResultsA total of 8341 records were identified through electronic searches and 35 and 54 studies were included in the clinical effectiveness and cost-effectiveness reviews respectively. There was a high apparent correlation between My5-FU, HPLC and LC-MS/mass spectrometer but upper and lower limits of agreement were –18% to 30%. Median OS were estimated as 19.6 [95% confidence interval (CI) 17.0 to 21.0] months for PK versus 14.6 (95% CI 14.1 to 15.3) months for BSA for 5-FU + folinic acid (FA); and 27.4 (95% CI 23.2 to 38.8) months for PK versus 20.6 (95% CI 18.4 to 22.9) months for BSA for FOLFOX6 in metastatic colorectal cancer (mCRC). PK versus BSA studies were generalisable to the relevant populations. We developed cost-effectiveness models for mCRC and H&N cancer. The base case assumed a cost per My5-FU assay of £61.03. For mCRC for 12 cycles of a oxaliplatin in combination with 5-fluorouracil and FA (FOLFOX) regimen, there was a quality-adjusted life-year (QALY) gain of 0.599 with an incremental cost-effectiveness ratio of £4148 per QALY. Probabilistic and scenario analyses gave similar results. The cost-effectiveness acceptability curve showed My5-FU to be 100% cost-effective at a threshold of £20,000 per QALY. For H&N cancer, again, given caveats about the poor evidence base, we also estimated that My5-FU is likely to be cost-effective at a threshold of £20,000 per QALY.LimitationsQuality and quantity of evidence were very weak for PK versus BSA dosing for all cancers with no randomised controlled trials (RCTs) using current regimens. For H&N cancer, two studies of regimens no longer in use were identified.ConclusionsUsing a linked evidence approach, My5-FU appears to be cost-effective at a willingness to pay of £20,000 per QALY for both mCRC and H&N cancer. Considerable uncertainties remain about evidence quality and practical implementation. RCTs are needed of PK versus BSA dosing in relevant cancers.FundingThe National Institute for Health Research Health Technology Assessment programme.

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Section: Identificationmentioning

confidence: 99%

Section: Identificationmentioning

confidence: 99%

Section: Identificationmentioning

confidence: 99%

Section: My5-fu Assaymentioning

confidence: 99%

Section: My5-fu Assaymentioning

confidence: 99%

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Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion

Freeman

Connock

Cummins³

et al. 2015

Health Technol Assess

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Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

et al. 2022

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Background The body composition of patients has been associated with tolerability and effectiveness of anticancer therapy. This study aimed to assess the influence of the skeletal muscle index (SMI) on the pharmacokinetics and toxicity of fluorouracil. Methods Patients treated in an oncological practice with fluorouracil‐based chemotherapy and undergoing therapeutic drug monitoring were retrospectively investigated. Computed tomography images were analyzed to measure abdominal skeletal muscle areas in Hounsfield units for the psoas major muscle, back and total skeletal muscle to determine the SMI. For the latter, an automated segmentation method was used additionally. SMI measures were tested as covariates on fluorouracil clearance in a population pharmacokinetic model. Furthermore, regression analyses were performed to analyze the influence of SMI measures on the probability of clinically relevant adverse events (CTCAE grades ≥ 2). Results Fluorouracil plasma concentrations of 111 patients were available. Covariate analyses showed significant improvements of the model fit by all SMI measures. However, interindividual variability of fluorouracil clearance was only slightly reduced, whereas the SMI of the back muscle showed the largest reduction (−1.1 percentage points). Lower SMI values of the back muscle increased the probability for polyneuropathy and lower SMI of the psoas increased the probability for fatigue. Conclusions Our results suggest that pharmacokinetics and toxicity of fluorouracil may be associated with specific SMI measures which deserve further investigation.

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Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5‐Fluorouracil Therapy

Beumer

Chu

Allegra

et al. 2018

Clin Pharma and Therapeutics

Self Cite

102

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5-Fluorouracil (5-FU) is dosed by body surface area, a practice unable to reduce the interindividual variability in exposure. Endorsed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), we evaluated clinical evidence and strongly recommend TDM for the management of 5-FU therapy in patients with colorectal or head-and-neck cancer receiving common 5-FU regimens. Our systematic methodology provides a framework to evaluate published evidence in support of TDM recommendations in oncology.

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Multicenter Evaluation of a Novel Nanoparticle Immunoassay for 5-Fluorouracil on the Olympus AU400 Analyzer

Cited by 45 publications

References 21 publications

Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion

Fluorouracil plasma monitoring: systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion

Influence of the skeletal muscle index on pharmacokinetics and toxicity of fluorouracil

Therapeutic Drug Monitoring in Oncology: International Association of Therapeutic Drug Monitoring and Clinical Toxicology Recommendations for 5‐Fluorouracil Therapy

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