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CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(02): 134-141
DOI: 10.1055/s-0043-1776294
Original Article

Therapeutic Drug Monitoring of 5-Fluorouracil in Head and Neck Cancer Patients: An Interventional Pilot Study

P. Sharmila Nirojini
1   Department of Pharmacy Practice, Swamy Vivekanandha College of Pharmacy (Affiliated to the Dr. M.G.R. Medical University), Namakkal, Tamil Nadu, India
,
N.K. Bhuvaneshwari
2   Pharm D Intern, Swamy Vivekanandha College of Pharmacy (Affiliated to the Dr. M.G.R. Medical University), Namakkal, Tamil Nadu, India
,
N. Dharsshini 
2   Pharm D Intern, Swamy Vivekanandha College of Pharmacy (Affiliated to the Dr. M.G.R. Medical University), Namakkal, Tamil Nadu, India
,
S. Dhivya Bharathi
2   Pharm D Intern, Swamy Vivekanandha College of Pharmacy (Affiliated to the Dr. M.G.R. Medical University), Namakkal, Tamil Nadu, India
,
K. Velavan
3   Radiation Oncologist, Erode Cancer Centre, Erode, Tamil Nadu, India
› Author Affiliations Funding None declared.
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Abstract

Introduction 5-fluorouracil (5-FU) is a crucial agent in treating various types of cancer, particularly recurrent head and neck cancers (HNCs). According to prior studies, individuals who underwent therapeutic drug monitoring (TDM) based 5-FU dosage adjustments showed significantly higher response rates and experienced fewer adverse events compared with those who received the standard 5-FU administration. This study aims to enhance our understanding of the overall clinical outcomes in patients with recurrent HNCs who received 500 mg of 5-FU through a pharmacokinetic (PK) analysis.

Objectives Our objectives are to conduct TDM in selected HNC patients and observe individual PK responses, efficacy, tolerability, and drug toxicity.

Materials and Methods We enrolled a total of 12 patients with recurrent metastatic HNC, and all of them received a fixed dose of 500 mg with cisplatin in a 21-day cycle. During cycle II or III, we analyzed the blood concentrations and PK parameters of 5-FU using the liquid chromatography and mass spectrometry (LC–MS) technique. Notably, we calculated the Concentration maximum (Cmax), time at which the concentration reaches maxiumum (Tmax), Half life of the drug (T1/2), and area under the curve (AUC) for the 500-mg dose of 5-FU, as the PK data for this particular dose were unavailable, making our study uniquely valuable for assessing efficacy and toxicity.

Results Within the study group, 83.33% obtained an average AUC range of 1,000 to 3,000 h/µg/mL. Out of this group, 41.66% showed a partial response, 33.33% experienced disease progression, and 25% remained stable during the therapy. One patient had an AUC below the expected value (832.21 h/µg/mL), while another had an overexposed AUC value (5726.87 h/µg/mL), resulting in a poor clinical outcome. After interpreting the results, suggestions for dosage adjustments were made to the clinician.

Conclusion From our interventional study, it is evident that at a flat dose of 500 mg, PK-based individual dosage regimens play a superior role in managing advanced cancer patients with minimal toxicities. This PK analysis showed us clarity on the outcomes of 5-FU at a 500-mg dose.

Keywords

5-fluorouracil - therapeutic drug monitoring - head and neck cancer - dosage adjustments

Author Contributions

N.K.B, N.D., and S.D.B. were responsible for the concept and design of the study, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and literature search. Critical revision of the manuscript for important intellectual content was done by K.V. and P.S.N. They also provided administrative, technical, or logistic support. PSN contributed to design the study protocol and supervised the study.


Statement

The manuscript has been read and approved by all the authors, and the requirements for authorship have been met.


Patient Consent

The consent from the patient has been taken to participate on this study.


Supplementary Material



Publication History

Article published online:
25 October 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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