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Medline ® Abstract for Reference 150

of 'Dosing of anticancer agents in adults'

150
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Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review.
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Freeman K, Saunders MP, Uthman OA, Taylor-Phillips S, Connock M, Court R, Gurung T, Sutcliffe P, Clarke A
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BMC Cancer. 2016;16:523. Epub 2016 Jul 25.
 
BACKGROUND: Pharmacokinetic guided dosing of 5-fluorouracil chemotherapies to bring plasma 5-fluorouracil into a desired therapeutic range may lead to fewer side effects and better patient outcomes. High performance liquid chromatography and a high throughput nanoparticle immunoassay (My5-FU) have been used in conjunction with treatment algorithms to guide dosing. The objective of this study was to assess accuracy, clinical effectiveness and safety of plasma 5-fluorouracil guided dose regimen(s) versus standard regimens based on body surface area in colorectal cancer.
METHODS: We undertook a systematic review. MEDLINE; MEDLINE In-Process&Other Non-Indexed Citations; EMBASE; Cochrane Library; Science Citation Index and Conference Proceedings (Web of Science); and NIHR Health Technology Assessment Programme were searched from inception to January 2014. We reviewed evidence on accuracy of My5-FU for estimating plasma 5-fluorouracil and on the clinical effectiveness of pharmacokinetic dosing compared to body surface area dosing. Estimates of individual patient data for overall survival and progression-free survival were reconstructed from published studies. Survival and adverse events data were synthesised and examined for consistency across studies.
RESULTS: My5-FU assays were found to be consistent with reference liquid chromatography tandem mass spectrometry. Comparative studies pointed to gains in overall survival and in progression-free survival with pharmacokinetic dosing, and were consistent across multiple studies.
CONCLUSIONS: Although our analyses are encouraging, uncertainties remain because evidence is mainly from outmoded 5-fluorouracil regimens; a randomised controlled trial is urgently needed to investigate new dose adjustment methods in modern treatment regimens.
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Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
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