title: Therapeutic drug monitoring of 5-fluorouracil.
abstract: For over 50 years, 5-FU has played a critical role in the systemic chemotherapy of cancer patients. 5-FU serves as the main backbone of combination chemotherapy for patients with colorectal cancer in both the adjuvant and metastatic disease settings. Herein, we review the current status of 5-FU therapeutic drug monitoring (TDM) and discuss its potential role in the clinical practice setting.
  
  
  
  PubMed and abstracts from the American Society of Clinical Oncology were searched up through September 2015 for clinical data relating to 5-FU TDM.
  
  
  
  5-FU dosing has been typically determined by using body surface area (BSA). However, it is now well established that BSA-based 5-FU dosing is correlated with a wide variation of 5-FU systemic exposure. Pharmacokinetic (PK) studies of 5-FU systemic exposure have shown a wide range of interpatient variation of 5-FU plasma drug levels. Over the past 30 years, increasing efforts have been placed on optimizing 5-FU dosing with the main goals of increasing antitumor efficacy while reducing drug-associated toxicity. There is growing evidence to show that 5-FU dosing based on plasma 5-FU drug level is feasible and that 5-FU TDM can improve clinical outcomes by improving efficacy of 5-FU-based combination regimens and reducing toxicities.
  
  
  
  Dose adjustment of 5-FU is feasible, and PK-based dosing can significantly improve clinical outcomes by reducing toxicities and improving efficacy.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, 5150 Centre Ave., Fifth Floor, Pittsburgh, PA, 15232, USA. leejj@upmc.edu.|Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. leejj@upmc.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, 5150 Centre Ave., Fifth Floor, Pittsburgh, PA, 15232, USA.|Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.|Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, 5150 Centre Ave., Fifth Floor, Pittsburgh, PA, 15232, USA.|Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Chu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil