5-Fluorouracil toxicity and dihydropyrimidine dehydrogenase enzyme: implications for practice

Area of Science:

• Oncology
• Pharmacogenomics

Background:

• 5-fluorouracil (5-FU) is a cornerstone chemotherapy agent for solid tumors.
• Dihydropyrimidine dehydrogenase (DPD) is critical for 5-FU metabolism and clearance.
• DPD deficiency, often due to the c.1905+1G>A mutation, can lead to severe 5-FU toxicity.

Purpose of the Study:

• To highlight the clinical significance of DPD deficiency in 5-FU chemotherapy.
• To emphasize the importance of patient assessment and education regarding 5-FU toxicity.
• To inform healthcare providers about managing 5-FU-related adverse events.

Main Methods:

• Review of existing literature on 5-FU metabolism and DPD deficiency.
• Analysis of clinical implications of DPD deficiency.
• Discussion of current management strategies for 5-FU toxicity.

Main Results:

• The c.1905+1G>A mutation is the most common cause of DPD deficiency.
• Routine genetic screening for DPD deficiency is not cost-effective for the general population.
• Supportive care and patient education are primary methods for managing 5-FU toxicity.

Conclusions:

• Despite low prevalence, DPD deficiency poses a significant risk for severe 5-FU toxicity.
• Proactive patient and caregiver education is essential for early recognition and management of adverse effects.
• Oncology practitioners and nurses play a vital role in optimizing 5-FU therapy safety.