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Therapeutic drug monitoring of 5-fluorouracil

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Abstract

Purpose

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.

Method

PubMed and abstracts from the American Society of Clinical Oncology were searched up through September 2015 for clinical data relating to 5-FU TDM.

Results

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.

Conclusion

Dose adjustment of 5-FU is feasible, and PK-based dosing can significantly improve clinical outcomes by reducing toxicities and improving efficacy.

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Acknowledgments

This review was supported in part by NCI UM1-CA186690. This project used the UPCI Cancer Pharmacokinetics and Pharmacodynamics Facility (CPPF), which was supported in part by NCI P30-CA147904.

Author information

Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, 5150 Centre Ave., Fifth Floor, Pittsburgh, PA, 15232, USA

    James J. Lee, Jan H. Beumer & Edward Chu

  2. Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    James J. Lee, Jan H. Beumer & Edward Chu

  3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA

    Jan H. Beumer

Authors
  1. James J. Lee
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  2. Jan H. Beumer
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  3. Edward Chu
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Correspondence to James J. Lee.

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Lee, J.J., Beumer, J.H. & Chu, E. Therapeutic drug monitoring of 5-fluorouracil. Cancer Chemother Pharmacol 78, 447–464 (2016). https://doi.org/10.1007/s00280-016-3054-2

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  • DOI: https://doi.org/10.1007/s00280-016-3054-2

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