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
