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Medline ® Abstract for Reference 150

of 'Dosing of anticancer agents in adults'

Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review.
Freeman K, Saunders MP, Uthman OA, Taylor-Phillips S, Connock M, Court R, Gurung T, Sutcliffe P, Clarke A
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.
Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.