title: Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Karoline
authors.initials: K
authors.lastname: Freeman
authors.affiliation: The Christie, 550 Wilmslow Road, Manchester, M20 4BX, UK.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Saunders
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Olalekan A
authors.initials: OA
authors.lastname: Uthman
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Taylor-Phillips
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. m.connock@warwick.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Connock
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Court
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Tara
authors.initials: T
authors.lastname: Gurung
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Sutcliffe
authors.affiliation: Division of Health Sciences, Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK.
authors.forename: Aileen
authors.initials: A
authors.lastname: Clarke
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005472:Fluorouracil / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D009367:Neoplasm Staging; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil
keywords: 5-fluorourcil; Colorectal cancer; Dose algorithms; Pharmacokinetic monitoring