Personalizing 5-FU Treatment in Head and Neck Cancer: A TDM Pilot Study

Dharsshini

Clinical Pharmacy Intern, Kauvery Hospitals, Trichy

Introduction

5 – Fluorouracil (5-FU) is a crucial agent in treating various types of cancers, particularly recurrent head and neck cancers (HNC). 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 to those who received standard 5-FU administration. This study aims to enhance our understanding of the overall clinical outcomes in patients with recurrent Head and Neck Cancers who received 500mg of 5-Fluorouracil through Pharmacokinetic analysis. This pilot investigation enhances comprehension of disease progression, survival rate, and the efficacy of chemotherapy in certain populations while providing updated information to clinicians on the safe and effective utilization of 5-Fluorouracil. The main focus of this study is to examine the correlation between pharmacokinetic data and its impact on both treatment effectiveness and potential side effects when administering a constant 500mg dose of 5-Fluorouracil through intravenous infusion over 8 hours.

It’s important to note that the actual treatment regimen involves a 2-day intravenous infusion of 5-FU + cisplatin, repeated every 21 days, with cisplatin playing a significant role in overall clinical outcomes. However, this evaluation specifically concentrates on observing the pharmacokinetic data of 5-FU at a flat dose of 500mg.

Objectives

Our objectives are to conduct Therapeutic Drug Monitoring (TDM) in selected Head and Neck cancer patients and observe individual pharmacokinetic 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 500mg with Cisplatin in a 21-day cycle. During Cycle II or Cycle III, we analyzed the blood concentrations and Pharmacokinetic parameters of 5-FU using the LCMS technique. Notably, we calculated Cmax, tmax, T1/2, and AUC for the 500mg 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 1000 to 3000 h/g/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/g/mL), while another had an overexposed AUC value (5726.87 h/g/mL), resulting in a poor clinical outcome. After interpreting the results, suggestions for dosage adjustments were suggested to the clinician.

Discussion

In this study, 12 recurrent head and neck cancer patients diagnosed with Ca. tongue (4), Ca. oropharynx (4), Ca. buccal mucosa (2), Ca. tonsil (1), and Ca. oesophagus (1) in palliative care who underwent combination chemotherapy of cisplatin and 5-fluorouracil were chosen. The age group lies between 45 and 75 years old. We demonstrate that raising the dosage in under-dosed individuals may assist in minimizing toxicities and complaints from the present cycle to subsequent cycles in progressing malignancies. At the initial cycle, a flat 5-FU dose of 500 mg was administered, and no difference in terms of the 5-FU combination was observed. However, all the patients received 500mg of 5-FU + cisplatin on day 1 and 1000mg of 5-FU + cisplatin on day 2 as a cumulative total regimen for a 21-day cycle. As a reminder, for this study, individual dose adjustment was based on systemic exposure measured from TDM. An average AUC range of 1000 to 3000 h/g/mL was obtained in 83.33 % of the group, with two exceptions. One was under the expected AUC (832.21 h/g/mL) and one had an overexposed AUC value (5726.87 h/g/mL). Both cases showed wide variability in pharmacokinetic parameters.

Conclusion

From our interventional study, it is evident that at a flat dose of 500mg, pharmacokinetic-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 500mg dose.

Dharsshini

Clinical Pharmarcy – Intern

Personalizing 5-FU Treatment in Head and Neck Cancer: A TDM Pilot Study