Freeman, Karoline, Saunders, Mark P., Uthman, Olalekan A., Taylor-Phillips, Sian, Connock, M., Court, Rachel A., Gurung, T., Sutcliffe, P. (Paul) and Clarke, Aileen (2016) Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review. BMC Cancer, 16 (1). doi:10.1186/s12885-016-2581-x ISSN 1471-2407.

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Abstract

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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences > Population, Evidence & Technologies (PET) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Colon (Anatomy) -- Cancer -- Chemotherapy, Rectum -- Cancer -- Chemotherapy, Pharmacokinetics
Journal or Publication Title:	BMC Cancer
Publisher:	BioMed Central Ltd.
ISSN:	1471-2407
Official Date:	25 July 2016
Dates:	Date Event 25 July 2016 Published 19 July 2016 Accepted 2 December 2016 Submitted
Volume:	16
Number:	1
DOI:	10.1186/s12885-016-2581-x
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	29 July 2016
Date of first compliant Open Access:	1 August 2016
Funder:	National Institute for Health Research (Great Britain) (NIHR), University Hospitals Birmingham NHS Foundation Trust
Grant number:	13/111/01 (NIHR)

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