UPFRONT DPD DEFICIENCY DETECTION TO SECURE 5-FU ADMINISTRATION: PART 2- APPLICATION TO HEAD-AND-NECK CANCER PATIENTS

Area of Science:

• Pharmacogenomics
• Oncology
• Clinical Pharmacology

Background:

• Dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for 5-fluorouracil (5-FU) toxicity.
• Functional testing for DPD deficiency can categorize patients into extensive metabolizers (EM) or poor metabolizers (PM).
• Tailoring 5-FU dosage based on DPD status is crucial for patient safety.

Purpose of the Study:

• To evaluate the implementation of DPD-based adaptive dosing in routine clinical practice for head-and-neck cancer patients.
• To assess the impact of DPD deficiency screening on 5-FU related toxicities.
• To determine if adaptive dosing affects the clinical efficacy of 5-FU.

Main Methods:

• Observational study of 218 adult patients treated with 5-FU.
• DPD deficiency screening using UH2/U ratio in plasma to identify PM patients.
• Adaptive dosing of 5-FU based on DPD status (PM patients received 20-50% reduced dosage).

Main Results:

• 20% of patients (9%) were identified as PM and received reduced 5-FU dosing.
• Female gender was associated with a higher risk of being PM.
• Severe toxicities were significantly lower (5% early, 12.8% overall) compared to historical data for standard 5-FU dosing.
• No statistically significant difference in clinical efficacy was observed between EM and PM groups despite dose reduction.

Conclusions:

• Upfront DPD deficiency detection and adaptive dosing significantly reduce 5-FU related toxicities in clinical practice.
• This strategy allows for safe and effective 5-FU treatment in head-and-neck cancer patients.
• DPD-based dosing is a valuable tool for personalized cancer therapy.